Download American Society of Echocardiography Recommendations for

GUIDELINES AND STANDARDS
American Society of Echocardiography
Recommendations for Performance,
Interpretation, and Application of Stress
Echocardiography
Patricia A. Pellikka, MD, Sherif F. Nagueh, MD, Abdou A. Elhendy, MD, PhD,
Cathryn A. Kuehl, RDCS, and Stephen G. Sawada, MD, Rochester, Minnesota; Houston,
Texas; Marshfield, Wisconsin; and Indianapolis, Indiana
TABLE OF CONTENTS
Methodology...... ..............................................1021
Imaging Equipment and Technique............1021
Stress Testing Methods...... ............................1022
Training Requirements and Maintenance
of Competency...... .....................................1023
Image Interpretation......................................1024
Table 1. Normal and Ischemic
Responses for Various Modalities
of Stress........................................................1025
Quantitative Analysis Methods.....................1025
Accuracy...... .....................................................1026
False-negative Studies...... ..............................1026
False-positive Studies...... ...............................1027
Assessment of Myocardial Viability.............1027
Assessment of Patients With Dyspnea,
Pulmonary Hypertension, and
Valvular Heart Disease...... ........................1028
Dyspnea............................................................1028
Pulmonary Hypertension..............................1029
Mitral Valve Disease...... .................................1029
Aortic Valve Disease...... .................................1029
Evaluation of Prosthetic Valves....................1030
Stress Echocardiography for Risk
Stratification................................................1030
Table 2. Summary of Studies Evaluating
the Value of Stress Echocardiography
in Predicting Outcome...... ........................1031
Table 3. Stress Echocardiography
Predictors of Risk.......................................1032
Women..............................................................1032
After Acute Myocardial Infarction...... .........1032
Elderly...............................................................1033
Patients With Diabetes Mellitus...... .............1033
Before Noncardiac Surgery...... .....................1033
After Coronary Revascularization...... .........1033
Patients With Angina...... ...............................1033
Comparison With Radionuclide Imaging...... ....1033
Recent and Future Developments...... .........1034
Strain and Strain Rate Echocardiograpy...... ......1034
Three-Dimensional Echocardiography...... ........1034
Myocardial Contrast Perfusion Imaging...... ......1034
Summary...... ....................................................1034
References........................................................1034
A
dvances since the 1998 publication of the
Recommendations for Performance and Interpretation of Stress Echocardiography1 include improvements in imaging equipment, refinements in stress
testing protocols and standards for image interpretation, and important progress toward quantitative
analysis. Moreover, the roles of stress echocardiography for cardiac risk stratification and for assessment of myocardial viability are now well documented. Specific recommendations and main points
are identified in bold.
METHODOLOGY
Imaging Equipment and Technique
Digital acquisition of images has evolved from the
days of stand-alone computers that digitized analog
video signals to the current era in which ultrasound
systems have direct digital output.2 This has resulted
in significant improvements in image quality. Many
ultrasound systems have software to permit acquisition and side-by-side display of baseline and stress
images. However, transfer of images to a computer
workstation for offline analysis is preferred as the
ultrasound equipment can be continuously used for
imaging. Network systems with large archiving capacity allow retrieval of serial stress examinations.
Digital image acquisition permits review of multiple
cardiac cycles with stress, which maximizes accuracy of interpretation. Videotape recordings are
recommended as a backup.
Advances in imaging technology have improved
endocardial border visualization and increased the
From the aDivision of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Foundation; bMethodist DeBakey Heart
Center, Houston (S.F.N.); cMarshfield Clinic (A.A.E.); and dIndiana University School of Medicine (S.G.S.).
Reprint requests: Patricia A. Pellikka, MD, Mayo Clinic, 200 First
St SW, Rochester, MN 55905 (E-mail: pellikka.patricia@
mayo.edu).
0894-7317/$32.00
Copyright 2007 by the American Society of Echocardiography.
doi:10.1016/j.echo.2007.07.003
1021
1022 Pellikka et al
feasibility of imaging. Tissue harmonic imaging
should be used for stress echocardiography
imaging. This reduces near-field artifact, improves
resolution, enhances myocardial signals, and is superior to fundamental imaging for endocardial border visualization.3 The improvement in endocardial
visualization achieved with harmonic imaging has
decreased interobserver variability and improved
the sensitivity of stress echocardiography.4,5
The availability of intravenous contrast agents for
left ventricular (LV) opacification represents another advance. When used in conjunction with
harmonic imaging, contrast agents increase the
number of interpretable LV wall segments, improve
the accuracy of less experienced readers, enhance
diagnostic confidence, and reduce the need for
additional noninvasive tests because of equivocal
noncontrast stress examinations.6-9 Opacification of
the LV cavity with contrast agents also improves the
potential for quantitative assessment of studies.
Contrast should be used when two or more
segments are not well visualized. With experience and well-defined protocols, contrast stress
echocardiography has been shown to be time-efficient.10
The baseline echocardiogram performed at
the time of stress echocardiography should
include a screening assessment of ventricular
function, chamber sizes, wall-motion thicknesses, aortic root, and valves unless this assessment has already been performed. This
examination permits recognition of causes of cardiac symptoms in addition to ischemic heart disease,
including pericardial effusion, hypertrophic cardiomyopathy, aortic dissection, and valvular heart disease.
Stress Testing Methods
Exercise stress testing. For patients who are
capable of performing an exercise test, exercise stress rather than pharmacologic stress is
recommended, as the exercise capacity is an
important predictor of outcome. Either treadmill or bicycle exercise may be used for exercise stress. Symptom-limited exercise according to a standardized protocol in which the
workload is gradually increased in stages is
recommended. The Bruce protocol is most commonly used for treadmill exercise echocardiography
and the expected exercise level for a given age and
sex can be expressed as functional aerobic capacity.11 Imaging is performed at rest and immediately
after completion of exercise.12 Bicycle stress echocardiography can be performed with either supine
or upright ergometry; an advantage is that imaging
can be performed during exercise. With a commonly used supine bicycle protocol, imaging is
performed at baseline, at an initial workload of 25
Journal of the American Society of Echocardiography
September 2007
W, at peak stress, and in recovery. The workload is
increased at increments of 25 W every 2 or 3
minutes.13 A higher initial workload may be appropriate for a younger patient.
Both types of exercise examinations provide valuable information for detection of ischemic heart
disease and assessment of valvular heart disease. The
workload and maximum heart rate achieved tend to
be higher with treadmill exercise; exercise blood
pressure is higher with supine bicycle exercise. If
assessment of regional wall motion is the only
objective, treadmill exercise is usually used. If additional Doppler information is desired, bicycle exercise offers the advantage that Doppler information,
in addition to assessment of regional wall motion,
can be evaluated during exercise.14
Pharmacologic stress testing. In patients who
cannot exercise, dobutamine and vasodilator stress
are alternatives. Although vasodilators may have
advantages for assessment of myocardial perfusion, dobutamine is preferred when the test
is based on assessment of regional wall motion. A graded dobutamine infusion starting at
5 ␮g/kg/min and increasing at 3-minute intervals to 10, 20, 30, and 40 ␮g/kg/min is the
standard for dobutamine stress testing.15,16 The
inclusion of low-dose stages facilitates recognition of viability and ischemia in segments with
abnormal function at rest, even if viability
assessment is not the main objective of the test.
End points are achievement of target heart rate
(defined as 85% of the age-predicted maximum heart
rate), new or worsening wall-motion abnormalities
of moderate degree, significant arrhythmias, hypotension, severe hypertension, and intolerable symptoms. Atropine, in divided doses of 0.25 to 0.5
mg to a total of 2.0 mg, should be used as
needed to achieve target heart rate. Atropine
increases the sensitivity of dobutamine echocardiography in patients receiving beta-blockers and in
those with single-vessel disease.17 The minimum
cumulative dose needed to achieve the desired heart
rate effect should be used to avoid the rare complication of central nervous system toxicity. Protocols
using atropine in early stages of the test, and accelerated dobutamine administration, have been
shown to be safe and to reduce infusion times.18,19
Patients given atropine at the 30-␮g/kg/min stage
reached target heart rate more quickly using lower
doses of dobutamine and with fewer side effects. A
beta-blocker may be administered to reverse the side
effects of dobutamine.20 Administration of betablockers at peak stress or during recovery may
increase test sensitivity.21
Both dobutamine and exercise echocardiography
result in a marked increase of heart rate. The
increment in systolic blood pressure is much less
with dobutamine compared with exercise. For both
Journal of the American Society of Echocardiography
Volume 20 Number 9
techniques, the induction of ischemia is related to
an increase in myocardial oxygen demand. Among
patients with normal dobutamine stress echocardiography results, the subgroup in whom target heart
rate is not achieved has a higher cardiac event rate.22
Achievement of target rate is an important goal of
testing and consideration should be given to holding
beta-blocker therapy on the day of testing until after
the test. However, in a patient with known coronary
artery disease (CAD), continuation of beta-blocker
therapy may be preferred, depending on the clinical
objectives of the test, which may include assessing
adequacy of therapy. Side effects (palpitations, nausea, headache, chills, urinary urgency, and anxiety)
are usually well tolerated, without the need for test
termination. The most common cardiovascular side
effects are angina, hypotension, and cardiac arrhythmias. Severe, symptomatic hypotension necessitating test termination occurs only rarely. Frequent
premature atrial or ventricular contractions occur in
about 10% of patients and supraventricular or ventricular tachycardias each occur in about 4% of
patients. Ventricular tachycardias are usually nonsustained and more frequently encountered in patients with a history of ventricular arrhythmias or
baseline wall-motion abnormalities. On the basis of
combined diagnostic and safety reports on dobutamine stress echocardiography, it is estimated that
ventricular fibrillation or myocardial infarction occurs in 1 of 2000 studies. Dobutamine stress echocardiography can safely be performed in patients
with LV dysfunct,23 aortic24 and cerebral25 aneurysms, and implantable cardioverter defibrillators.26
Dobutamine stress echocardiography can safely and
efficiently be performed under supervision by registered nurses.27
Vasodilator stress testing may be performed with
adenosine or dipyridamole.28 Atropine is routinely
used with vasodilator stress to enhance test sensitivity. The addition of handgrip at peak infusion enhances sensitivity. Vasodilator stress echocardiography usually produces a mild to moderate increase in
heart rate and a mild decrease in blood pressure.
The safety of high-dose (up to 0.84 mg/kg over 10
minutes) dipyridamole echocardiography tests has
been documented. Significant side effects and minor
but limiting side effects occur in about 1%. Major
adverse reactions have included cardiac asystole,
myocardial infarction, and sustained ventricular
tachycardia. Hypotension and/or bradycardia may
occur, but can be treated with aminophylline.29 The
duration of action of adenosine is shorter than
dipyridamole. Adenosine stress is used to assess
myocardial perfusion with contrast echocardiography, but it has not been widely used as a clinical
tool. Both adenosine and dipyridamole are contraindicated in patients with reactive airway obstruction
or significant conduction defects.
Pellikka et al 1023
Pacing stress testing. In patients with a permanent pacemaker, stress testing can be achieved by
increasing the pacing rate until the target heart rate
is reached. This technique can be used with or
without dobutamine. Recent studies have shown a
good accuracy of this technique in identifying
CAD30 and in predicting outcome.31
Transesophageal atrial pacing stress echocardiography is an efficient alternative for the detection of
CAD in patients unable to exercise.32 The catheter
may be placed orally or nasally after topical anesthesia. The cardiac pacing and recording catheter
(housed in a 10F sheath) is advanced by having the
patient swallow while in the left lateral decubitus
position. Pacing is initiated at 10/min above the
patient’s baseline heart rate starting at the lowest
current that provides stable atrial capture (approximately 10 mA). The pacing protocol consists of
2-minute stages with the paced heart rate being
increased to levels of 85% and 100%, respectively,
for prepeak and peak stress information.33 Images
are obtained at rest, the first stage, and prepeak and
peak heart rate. Wenckebach second-degree heart
block may occur, necessitating atropine administration. Termination of the stress test occurs with
achievement of age-predicted maximal heart rate,
new or worsening moderate regional wall-motion
abnormalities, greater than 2-mm horizontal or
downsloping S-T depression, or presence of intolerable symptoms, including moderate angina. The
advantage of pacing is the rapid restoration of
baseline conditions and heart rate on discontinuation of the atrial stimulus; this avoids a prolonged
state of ischemia.33 Side effects, except for mild
atrial arrhythmogenicity, are uncommon.
Training Requirements and Maintenance of
Competency
Interpretation of stress echocardiography requires
extensive experience in echocardiography and
should be performed only by physicians with specific training in the technique. It is recommended
that only echocardiographers with at least level-II
training and specific additional training in stress
echocardiography have responsibility for supervision and interpretation of stress echocardiograms.
To achieve the minimum level of competence for
independent interpretation, training should include
interpretation of at least 100 stress echocardiograms
under the supervision of an echocardiographer with
level-III training and expertise in stress echocardiography.34 To maintain competence, it is recommended that physicians interpret a minimum of 100
stress echocardiograms per year, in addition to
participation in relevant continuing medical education. It is recommended that sonographers perform
a minimum of 100 stress echocardiograms per year
to maintain an appropriate level of skill.35 These
1024 Pellikka et al
recommendations refer to routine stress echocardiograms for evaluation of CAD and not highly specialized studies such as evaluation of valvular disease or
myocardial viability, for which more experience and
higher volumes may be required for maintenance of
skills.
IMAGE INTERPRETATION
Visual assessment of endocardial excursion and wall
thickening is used for analysis of stress echocardiograms. The 2005 American Society of Echocardiography (ASE) recommendations suggested that either
a 16- or 17-segment model of the LV may be used.36
The 17-segment model includes an “apical cap,” a
segment beyond the level that the LV cavity is seen.
The 17-segment model is recommended if myocardial perfusion is evaluated or if echocardiography is
compared with another imaging modality. Function
in each segment is graded at rest and with
stress as normal or hyperdynamic, hypokinetic, akinetic, dyskinetic, or aneurysmal. Images from low or intermediate stages of dobutamine infusion or bicycle exercise should be
compared with peak stress images to maximize
the sensitivity for detection of coronary disease.37
The timing of wall motion and thickening should
also be assessed. Ischemia delays both the onset of
contraction and relaxation and slows the velocity of
contraction in addition to decreasing the maximum
amplitude of contraction. “Hypokinesis” can refer to
delay in the velocity or onset of contraction (“tardokinesis”) and reduction in the maximum amplitude of
contraction. The routine use of digital technology
enables assessment of abnormalities in the timing of
contraction (asynchrony). Differences in the onset of
contraction and relaxation of ischemic segments compared with normal segments may range from less than
50 to more than 100 milliseconds.38,39 The frame rates
used in current ultrasound systems have the necessary
temporal resolution to permit visual recognition of
asynchrony by the trained observer.40,41 Although
assessment of asynchrony is most accurate using a high
temporal resolution technique such as M-mode echocardiography, incorporation of visual assessment of
the timing of contraction contributes to improved
interobserver agreement.42 zWork stations used for
analysis of stress echocardiograms enable the interpreter to compare the timing of segmental contraction
on a frame-by-frame basis and allow the interpreter to
limit review to early systole where ischemia-induced
reduction in the speed of contraction may be best
appreciated.43,44
A normal stress echocardiogram result is
defined as normal LV wall motion at rest and
with stress. Resting wall-motion abnormalities, un-
Journal of the American Society of Echocardiography
September 2007
changed with stress, are classified as “fixed” and
most often represent regions of prior infarction.
Patients with fixed wall-motion abnormalities and
no inducible ischemia should not be considered as
having a normal study result. Abnormal study
findings include those with fixed wall-motion
abnormalities or new or worsening abnormalities indicative of ischemia. In addition to the
evaluation of segmental function, the global LV
response to stress should be assessed. Stressinduced changes in LV shape, cavity size, and
global contractility have been shown to indicate the presence or absence of ischemia.45,46
Although evaluation of right ventricular (RV) systolic function is often omitted, RV free wall asynergy
or lack of increase in tricuspid annular plane excursion during dobutamine stress are indicators of right
coronary or multivessel disease.47,48
The modality of stress and details of the stress test
itself should be considered in the interpretation of
normal and ischemic responses to stress. The report must include not only the baseline and
stress assessment of systolic function and segmental wall motion, but the protocol used, the
exercise time or dose of pharmacologic agent
used, the maximum heart rate achieved,
whether the level of stress was adequate, the
blood pressure response, the reason for test
termination, any cardiac symptoms during the
test, and electrocardiographic (ECG) changes
or significant arrhythmias. In the presence of
similar extents of CAD, stress-induced decrease in
ejection fraction (EF) or increase in end-systolic
cavity size are more commonly seen with exercise
than with dobutamine stress.46 Table 1 lists several
modalities of stress and the general responses of
regional and global function that are seen in healthy
individuals and in those with obstructive coronary
disease.32,33,46,49-59 The responses are described for
individuals with normal regional and global systolic
function in the resting state. An interpretive scheme
for those with resting regional wall-motion abnormalities is described in the section on myocardial
viability.
With modalities in which imaging is performed at various stages of stress, such as
dobutamine stress echocardiography or supine
bicycle stress echocardiography, images from
each stage of stress should be reviewed to
determine the heart rate and stage at which
ischemia first occurs. This information is useful in
perioperative risk stratification,60,61 as ischemia occurring at a low heart rate identifies patients at
highest risk of a perioperative event. Ischemic
threshold, calculated as the heart rate at which
ischemia first occurs, divided by 220 minus the
patient’s age, multiplied by 100, has been shown to
Journal of the American Society of Echocardiography
Volume 20 Number 9
Pellikka et al 1025
Table 1 Normal and ischemic responses for various modalities of stress
Regional
Stress method
Treadmill
Supine bicycle
Dobutamine
Vasodilator
Atrial pacing
Global
Normal response
Ischemic response
Postexercise increase
in function
compared with
rest
Peak exercise
increase in
function
compared with
rest
Increase in function,
velocity of
contraction
compared with
rest and usually
with low dose
Increase in function
compared with
rest
Postexercise decrease in
function compared
with rest
Decrease in
ESV, increase
in EF
Increase in ESV, decrease
in EF in multivessel or
L main disease
Peak exercise decrease
in function compared
with rest
Decrease in
ESV, increase
in EF
Increase in ESV and
decrease in EF in
multivessel or L main
disease
Decrease in function,
velocity of
contraction
compared with low
dose; may be less
compared with rest
Decrease in function
compared with rest
Greater decrease
in ESV,
marked
increase in EF
Often same as normal
response; infrequently,
ischemia produces
decreased EF; cavity
dilatation rarely occurs
Decrease in
ESV, increase
in EF
Often same as normal
response; occasionally,
ischemia produces
decreased EF; cavity
dilatation rarely occurs
No change or increase
ESV, decrease in EF
No change or
increase in
function
compared with
rest
Decrease in function
compared with rest
Normal response
Decrease in
ESV, no
change in EF
Ischemic response
EF, Ejection fraction; ESV, end-systolic volume; L, left.
correlate with the number of stenosed vessels and
with the EF response to exercise.62
Quantitative Analysis Methods
Visual assessment of LV wall thickening and motion
remains the standard method of interpretation of
stress echocardiography but is subject to interobserver and interinstitutional variability.63 Very good
reproducibility has been demonstrated in a clinical
setting by those with training and experience.64,65
Quantitative methods of analysis have been investigated in an effort to improve the reproducibility of
interpretation and enhance detection of coronary
disease, particularly by less experienced physicians.
Doppler assessment of global systolic and diastolic function, automated endocardial border detection using integrated backscatter, tissue Doppler
assessment of displacement, velocity, strain, and
strain rate have shown promise as clinically useful,
quantitative methods for detection of ischemia.
Doppler assessment of global diastolic function by
analysis of mitral inflow patterns is difficult at high
heart rates achieved during stress; assessment of
aortic systolic flow during stress lacks sensitivity.
The use of integrated backscatter to identify the
blood-endocardial interface is promising as an automated method for detection of ischemia during
dobutamine stress. Using this technique, in which
border detection may be enhanced by contrast
opacification of the ventricular cavity, endocardial
motion in successive frames throughout the cardiac
cycle can be color encoded to permit assessment of
the timing and location of regional abnormalities in
systolic and diastolic function.66,67
Doppler tissue imaging enables assessment of
high amplitude, low velocity signals from myocardium. Tissue velocities are assessed along the long
axis of the heart using apical views. Displacement,
strain, and strain rate can be derived from assessment of tissue velocities. Tissue velocity imaging
with dobutamine stress has shown comparable accuracy with wall-motion assessment by experts in
both single and multicenter trials.68,69 Tissue velocity imaging also improves the reproducibility and
accuracy of less experienced readers.70 Because of
the normal base to apex gradient in velocities,
detection of coronary disease requires derivation of
normal values for different myocardial segments.
Strain (measuring myocardial shortening or lengthening) and strain rate (measuring the rate of shortening or lengthening) provide better assessment of
myocardial contraction and relaxation than displacement or tissue velocities, which are more subject to
tethering and translational motion. Postsystolic
shortening, time to onset of regional relaxation, and
reduction in peak systolic strain and strain rate have
1026 Pellikka et al
been shown to be accurate markers of ischemia in
experimental71 and early clinical72-75 studies.
Adequate quality 2-dimensional (2D) images are a
prerequisite to successful quantitative analysis, even
using Doppler-based techniques. Like all Dopplerderived parameters, tissue velocities, strain, and
strain rate are influenced by the angle of interrogation so that off-axis apical images may result in
calculation errors. Recently introduced 2D echocardiographic methods for assessment of strain and
strain rate eliminate the angle dependency of these
Doppler-based techniques.76 In the future, quantitative methods may serve as an adjunct to expert
visual assessment of wall motion. The widespread
use of quantitative methods will require further validation and simplification of analysis
techniques.
ACCURACY
The 1998 ASE document on stress echocardiography
reported an average sensitivity of 88% (1265/1445)
and average specificity of 83% (465/563) for stress
echocardiography for the detection of coronary
artery stenosis (generally ⬎50% diameter stenosis by
angiography), based on data pooled from available
studies. Since then, additional studies evaluating the
accuracy of stress echocardiography have been performed, often in comparison with alternative imaging modalities. Studies comparing the accuracy
of nuclear perfusion imaging and stress echocardiography in the same patient population
have shown that the tests have similar sensitivities for the detection of CAD, but stress echocardiography has higher specificity.77-81 In a
pooled analysis of 18 studies in 1304 patients who
underwent exercise or pharmacologic stress echocardiography in conjunction with thallium or technetium-labeled radioisotope imaging, sensitivity and
specificity were 80% and 86% for echocardiography.
Corresponding values were 84% and 77% for myocardial perfusion imaging, respectively.79
In the current era, the specificity of all noninvasive imaging tests will be reduced by test verification
bias.82 A diminishing number of patients with normal or negative noninvasive examinations are subjected to angiography leading to reduction in the
apparent specificity of the noninvasive method
when angiography is used as the reference standard.
The comparatively high specificity of stress
echocardiography contributes to its use as a
cost-effective diagnostic method, particularly
in populations in which alternative stress testing methods have higher false-positive rates.
False-negative Studies
With few exceptions, the causes of false-negative
studies are not unique to stress echocardiography
Journal of the American Society of Echocardiography
September 2007
but are also seen with other noninvasive methods.
Suboptimal stress is a primary cause of false-negative
studies.83 An adequate level of stress is frequently
defined as achievement of 85% or more of the
patient’s age-predicted maximal heart rate for exercise or dobutamine stress and/or a rate-pressure
product of 20,000 or more for exercise testing.
Although these thresholds are not well validated, the
importance of increasing heart rate and rate-pressure product is well supported by the linear relationship between myocardial oxygen consumption and
these hemodynamic parameters. Inadequate exercise capacity and the use of beta-blockers are two
common causes of inadequate stress. Pharmacologic
stress and atrial pacing are suggested alternatives in
those who cannot exercise. Of the nonexercise
methods, the highest heart rates and sensitivity may
be achieved with atrial pacing.33,84 The use of
atropine substantially enhances the sensitivity of
dobutamine stress in the setting of beta-blockade17
and may be required to overcome Wenckebach
heart block during atrial pacing.32
The results of small comparative studies of treadmill and supine bicycle exercise echocardiography
suggest that imaging during peak exercise may
permit detection of ischemic wall-motion abnormalities in some cases when posttreadmill exercise
imaging produces negative findings.85,86 However,
workloads achieved are usually higher with treadmill exercise, partially offsetting the advantage of
peak exercise imaging.
As with other forms of stress testing, false-negative stress echocardiographic examination results
are also more common in patients with single-vessel
disease or disease of the left circumflex artery
because of the smaller amount of myocardium supplied.87 Supine bicycle exercise test has higher
sensitivity for detection of left circumflex disease.88,89 Routine use of apical long-axis views may
also decrease false-negative study results in those
with left circumflex disease.
Detection of ischemia is more difficult in patients with concentric remodeling, characterized
by small LV cavity volume and increased relative
wall thickness.90 False-negative studies in patients
with concentric remodeling may be more common with dobutamine stress than with other
methods. The prominent global hyperkinesis and
reduction of diastolic and systolic volumes that
occur with dobutamine stress (Table 1) may make
detection of isolated wall-motion abnormalities
more challenging. In addition, in patients with
concentric remodeling, dobutamine may lower
wall stress and myocardial oxygen consumption,
reducing the frequency of induction of ischemia.91 Finally, the hyperdynamic state accompanying significant aortic or mitral regurgitation may
make detection of ischemia more difficult.92
Journal of the American Society of Echocardiography
Volume 20 Number 9
False-positive Studies
False-positive stress echocardiogram findings can be
attributed to induction of ischemia in the absence of
epicardial coronary obstruction, or to nonischemic
causes of abnormal wall-motion responses to
stress.93 Abnormalities in regional function with
stress can occur in the absence of epicardial coronary artery obstruction if myocardial perfusion reserve is inadequate to meet myocardial oxygen
demand. Examples include global or regional LV
dysfunction in the case of hypertensive response to
stress94 or apical hypokinesis or other wall-motion
abnormalities in the case of hypertrophic cardiomyopathy with or without dynamic LV outflow tract
obstruction.95 Myocardial perfusion reserve can be
reduced in cardiac disorders with microvascular
involvement, including patients with LV hypertrophy, syndrome X, diabetes mellitus, myocarditis,
and idiopathic cardiomyopathy. Epicardial coronary
spasm may cause ischemia in the absence of fixed,
obstructive disease; spasm has been reported with
both exercise and dobutamine stress.
Wall-motion responses to exercise may be abnormal in patients with hypertension or underlying
cardiomyopathy in the absence of ischemia. Exercise may result in worsening of regional and global
systolic function in myopathic ventricles. Abnormal
global responses to stress are common in patients
with long-standing hypertension.96,97 The abnormal
wall-motion response of some patients with longstanding hypertension may be a result of underlying
cardiomyopathy even in the absence of LV hypertrophy or depression of resting systolic function.98,99
The effects of tethering on the assessment of
regional wall motion can lead to false-positive studies. The absence of radial motion of the mitral
annulus can lead to a reduction in motion of adjacent basal inferior and basal inferoseptal segments
by the tethering effect of the stationary annulus.93
This effect can be more pronounced in patients with
annulus calcification and previous mitral valve replacement.
Abnormal ventricular septal motion related to left
bundle branch block, RV pacing, and post-open
heart surgery can sometimes be confused with
ischemia-induced abnormalities. In these situations,
abnormal septal motion is usually present at rest.
Difficulty in determining the presence of ischemia
may occur if worsening of these abnormalities occurs during stress. Assessment of wall thickening
and the recognition that ischemia-induced wall-motion abnormalities should follow a typical coronary
distribution pattern may help to distinguish septal
dyssynchrony from ischemia.100-102 In addition, septal dyssynchrony may result in worsening of septal
perfusion and wall thickening at high heart rates in
the absence of coronary obstruction.
Pellikka et al 1027
ASSESSMENT OF MYOCARDIAL VIABILITY
Stress echocardiography has emerged as an important
modality for the assessment of patients with CAD and
LV systolic dysfunction. Multicenter studies have
shown worse outcome when viable myocardium was
identified by stress echocardiography but the patient
was not revascularized.103,104 Viable myocardium refers to reversible dysfunctional myocardium resulting
from CAD. However, the determination of contractile
reserve in patients with nonischemic cardiomyopathy
can also provide useful information as to myocardial
recovery of function105 and likelihood of response to
beta-blocker therapy.106
Reversible myocardial dysfunction in the setting of
chronic CAD has been referred to as “hibernating
myocardium.” Earlier descriptions of this entity emphasized the presence of a match between the decrease in myocardial perfusion and the presence of
regional dysfunction. However, more recent studies
have shown that contractility may be reduced despite
the presence of normal or only moderately reduced
myocardial perfusion at rest. This suggests that repetitive episodes of myocardial ischemia are a cause of
chronic dysfunction. In myocardium with reduced
perfusion at rest, structural and functional changes that
can occur include interstitial fibrosis, glycogen accumulation, loss of contractile proteins, cellular remodeling, higher calcium sensitivity of myocyte contractility, and attenuation of beta-receptor signaling.107-110
With delay in revascularization, these myocardial
changes may progress to a more advanced stage with
a lower likelihood of functional recovery.111
Most stress echocardiography protocols are centered on the detection of contractile reserve and
have used inotropic stimulation with dobutamine.
However, other modalities of stress echocardiography have been applied, including exercise, postpremature ventricular contraction stimulation, enoximone, and low-dose dipyridamole.
In comparison with the assessment of viability using
nuclear perfusion tracers or contract echocardiography, a lower extent of interstitial fibrosis and greater
percentage of viable myocytes are needed for the
detection of contractile reserve by dobutamine echocardiography.107 This probably accounts for the higher
sensitivity but lower specificity of myocardial perfusion imaging compared with dobutamine echocardiography in the detection of viable myocardium.
Both low- and high-dose protocols have been shown
to be useful for detection of viability. Earlier studies
examined low-dose dobutamine, whereas other investigators emphasized the importance of reaching at
least 85% of target heart rate in an attempt to uncover
the presence of ischemia. Wall thickness should be
assessed on the resting echocardiographic images.
Segments that are thinned (ⱕ0.5 or 0.6 cm) and bright
(likely a result of advanced fibrosis) rarely recov-
1028 Pellikka et al
er.112,113 It is also useful to examine the mitral inflow
pattern, particularly in patients who have received
adequate medical therapy at the time of imaging. A
pattern of restrictive LV filling is associated with few
viable segments and a low likelihood of functional
recovery after revascularization.114 Baseline imaging
should include assessment for the presence of significant valvular disease that may alter surgical plans. After
adequate baseline data have been obtained, dobutamine infusion is begun.
An initial infusion of dobutamine at 2.5 ␮g/kg/
min, with gradual increase to 5, 7.5, 10, and 20
␮g/kg/min, is frequently used.115 Because many of
these patients have multivessel disease, moderate to
severely depressed LV systolic function, and an
arrhythmogenic substrate, vigilant monitoring is indicated. The absence of functional improvement in
akinetic segments would then trigger termination of
the test, because this response signifies a very low
likelihood of functional recovery in these segments.
The presence of worsening of function in hypokinetic segments should likewise trigger termination
of the infusion. Alternatively, functional improvement in the absence of untoward side effects would
lead to an escalation of the drip rate to 40 ␮g/kg/min
and, if needed, atropine injection. The advantage of
the higher dose dobutamine is the potential to elicit
ischemia. Dysfunctional myocardium responds to
dobutamine in one of 4 ways that are most likely to
be appreciated when the response to both high and
low doses of dobutamine are considered. These
responses include biphasic response (augmentation
at a low dose followed by deterioration at a higher
dose), sustained improvement (improvement in
function at a low dose without deterioration at
higher doses), worsening of function, and no change
in function.
The sensitivity of dobutamine echocardiography
in predicting functional recovery (which varies depending on the protocol used) ranges from 71% to
97%, with a specificity ranging from 63% to 95%.116
The highest sensitivity for detection of viability
is noted when improvement at low-dose dobutamine echocardiography is considered; highest specificity is achieved when a biphasic
response occurs.117 Patients with a large area of
viable myocardium (⬎25% of LV) have a high likelihood of improvement in EF and a better outcome
after revascularization compared with patients with
less or no contractile reserve.118 Although presence of viability has been defined in various
ways, it is recommended that improvement by
at least one grade in two or more segments be
demonstrated. A substantial amount of viable myocardium detected by low-dose dobutamine echocardiography has been shown to prevent ongoing
remodeling after revascularization and to be associated with persistent improvement of heart failure
Journal of the American Society of Echocardiography
September 2007
symptoms and a lower incidence of cardiac
events.119
Additional echocardiographic methods used to
identify viable myocardium have included assessment of the microcirculation with contrast echocardiography, and myocardial tissue characterization
using integrated backscatter. For both approaches,
data are acquired at baseline and with vasodilators or
dobutamine infusion. In the future, quantitative
methods for analysis of regional function may improve viability assessment. Preliminary studies suggest that assessment of strain rate and strain can
enhance detection of viable myocardium.120-122
ASSESSMENT OF PATIENTS WITH DYSPNEA,
PULMONARY HYPERTENSION, AND
VALVULAR HEART DISEASE
Dyspnea
Stress echocardiography is useful for the evaluation of patients with dyspnea of possible
cardiac origin.123 In addition to data on the presence, severity, and extent of myocardial ischemia,
LV and left atrial volumes, EF, presence of LV
hypertrophy and/or valvular disease, a baseline
echocardiogram can identify the presence of pulmonary hypertension or abnormal LV relaxation and
elevated filling pressures. In some cases, the diagnosis of a cardiac origin can be ascertained by the
findings of the baseline resting images and stress
testing may not be needed. Exercise using a supine
bike is the recommended modality as it allows the
acquisition of Doppler recordings during exercise.
Doppler assessment of the mitral inflow velocities
should be assessed at rest, during exercise, and in
recovery when the E and A velocities are no longer
fused. Doppler recordings should be acquired at a
sweep speed of 100 mm/s. The ratio of mitral E
(peak early diastolic velocity) to mitral annulus early
diastolic velocity (e’) can be used to estimate LV
filling pressures at rest and exercise. Healthy individuals will show a similar increase in mitral E and
annular e’, such that the ratio has no or only minimal
change with exercise.124 Patients with impaired LV
relaxation develop an increase in LV filling pressures
with exercise as a result of tachycardia and the
abbreviated diastolic filling period. Accordingly, mitral peak E velocity increases. However, given the
minimal effect of preload on annular e’ in the
presence of impaired relaxation, annular e’ remains
reduced. Therefore, E/e’ ratio increases with exercise in patients with diastolic dysfunction.125,126
This approach has been validated against invasive
measurements for identifying an elevated exercise
mean LV diastolic pressure.126 Limitations to the
above methodology include atrial fibrillation, tech-
Journal of the American Society of Echocardiography
Volume 20 Number 9
nically challenging imaging windows, and limited
validation. Furthermore, it remains to be seen how
abnormalities in regional function influence the
accuracy of a single site measurement of e’.
Pulmonary Hypertension
Transthoracic Doppler echocardiography permits a
reliable estimation of pulmonary artery pressures,
detection of cardiac causes of pulmonary hypertension, and changes in RV and LV volumes and function with the disease and its treatment.127 Exercise
may be useful in patients with pulmonary hypertension to gain insight into RV and LV function128,129
and the changes in stroke volume with exercise.130
Some patients with a normal pulmonary artery pressure at rest have marked increase with exercise; the
prognostic significance of this has not been defined.
The normal response to exercise has been assessed
in healthy individuals and in young male athletes.131
Highly trained male athletes have been found to
have a Doppler-derived pulmonary artery systolic
pressure as high as 60 mm Hg with exercise.131
There are also published reports about the use of
exercise echocardiography in detecting asymptomatic gene carriers of familial primary pulmonary
hypertension,13 and identifying patients susceptible
to high-altitude pulmonary edema.132
Mitral Valve Disease
In patients with mitral valve disease, exercise testing
may provide insights regarding exertional symptoms
disproportionate to resting hemodynamics.133 It is
also useful in patients with severe lesions but no
symptoms; exercise-induced increase in pulmonary
artery systolic pressure to greater than 60 mm Hg
may be considered an indication for mitral valve
surgery (class IIA indication in 2006 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines for the Management of Patients with Valvular Heart Disease).134 Most of the
published studies used a supine bike protocol for
image acquisition. Mitral inflow is recorded with
pulsed wave Doppler (for mitral regurgitation) and
continuous wave Doppler (for mitral stenosis),
along with recording of tricuspid regurgitation velocity by continuous wave Doppler at rest and
during exercise.
For patients with mitral stenosis, stress
Doppler echocardiography is indicated in
asymptomatic patients with significant lesions based on hemodynamic calculations
obtained at rest, and for patients with symptoms disproportionate to resting Doppler hemodynamics (class I indication).134 At baseline and with stress, transmitral pressure
gradient and tricuspid regurgitation velocity
are obtained by continuous wave Doppler
using the modified Bernoulli equation. With
Pellikka et al 1029
proper alignment of the ultrasound beam with
transmitral flow, accurate Doppler-derived gradients can be obtained at rest and with exercise and
correlate well with invasively derived measurements.135 In sedentary patients, exercise-induced
dyspnea, along with an increase in mean transmitral pressure gradient to greater than 15 mm Hg
and pulmonary artery systolic pressure to greater
than 60 mm Hg, identifies patients with hemodynamically significant lesions that may benefit from
percutaneous valvotomy if anatomy is suitable and
mitral regurgitation is mild or less.134,136 When
exercise results in only minimal changes in transmitral pressure gradient but a marked increase in
pulmonary artery systolic pressure occurs, further
evaluation for underlying lung disease is indicated. In patients unable to exercise, dobutamine
stress may be used.137,138
Evaluation of mitral regurgitation is possible with
quantitative and semiquantitative color Doppler
methods.14,139 Exercise echocardiography has been
used to uncover the presence of severe mitral
regurgitation with exercise in patients with rheumatic mitral valve disease and only mild mitral
stenosis and regurgitation at rest.140 Likewise, exercise echocardiography is of value in identifying
hemodynamically significant dynamic mitral regurgitation in patients with LV systolic dysfunction. In
some patients, dynamic mitral regurgitation can
account for acute pulmonary edema and predicts
poor outcome.141 For patients with severe mitral
regurgitation and normal EF at rest, stress echocardiography can detect the presence of reduced LV
contractile reserve.142
Aortic Valve Disease
Dobutamine echocardiography is indicated in
the diagnostic evaluation of patients with LV
systolic dysfunction and low-gradient aortic
stenosis, defined as Doppler-derived aortic
valve area less than 1.0 cm2 and mean gradient
less than 30 mm Hg.134 In these patients, dobutamine is used to assess both the severity of
aortic stenosis and the presence of LV contractile reserve.143,144 The infusion begins at 5 ␮g/
kg/min and is increased at 5-minute intervals
to 10 and 20 ␮g/kg/min.
Dobutamine results in a larger increase of mean
pressure than transvalvular flow in patients with
severe aortic stenosis. Accordingly, aortic valve area
remains abnormally low indicating true aortic stenosis. On the other hand, dobutamine infusion results
in larger increments of flow rate and valve area in
patients with “functional” aortic stenosis, which is
primarily a result of reduced flow rate. In a recent
study, calculation of projected effective orifice area
improved the diagnostic accuracy of dobutamine
echocardiography in identifying patients with true
1030 Pellikka et al
aortic stenosis, with surgical inspection used as the
gold standard.145 Dobutamine echocardiography
provides important prognostic information in patients with LV systolic dysfunction and aortic stenosis, as surgery with aortic valve replacement appears
to improve outcome for most patients with LV
contractile reserve. In contrast, surgery is associated
with high mortality in the absence of contractile
reserve.146
For patients with chronic aortic regurgitation,
exercise testing may be considered to evaluate
functional capacity when symptoms are questionable, or before participation in athletic activities
(class IIA indications).134 Likewise, useful prognostic information may be obtained before surgery in patients with LV dysfunction (class IIB
indication).134 This is supported by a number of
studies with radionuclide angiography showing
abnormal EF (and change in EF) with exercise in
asymptomatic patients with aortic regurgitation.
However, the incremental value of exercise data
to LV dimensions and EF at rest is unclear. Stress
echocardiography is not indicated in clearly symptomatic patients with severe aortic regurgitation
or patients with depressed EF who should be
referred for surgery without stress testing.
Evaluation of Prosthetic Valves
Stress echocardiography has been applied to the
assessment of transvalvular gradients and flow in
prosthetic aortic valves. The majority of reports used
dobutamine147-149 but a few examined changes in
valvular hemodynamics with exercise.149
Although stress echocardiography has the potential to assess ventricular and prosthetic valvular
function in symptomatic patients with equivocal
findings at rest, the interpretation of Doppler gradients can be challenging given their dependence not
only on flow rate but the type and size of the
prosthetic valve. Additional data are needed to characterize normal responses for various prostheses.
STRESS ECHOCARDIOGRAPHY FOR RISK
STRATIFICATION
Stress echocardiography is a useful technique for the
risk stratification of patients with known or suspected CAD. This has been well documented in
numerous large studies in which follow-up was
obtained in consecutive patients referred for clinically indicated stress echocardiography. These studies have documented the prognostic use of the
test in patients with various pretest probabilities
of disease, symptoms, known CAD, prior coronary artery revascularization, or prior myocardial infarction and in asymptomatic patients
with risk factors for CAD. The prognostic value of
Journal of the American Society of Echocardiography
September 2007
the test has been shown to be maintained in patients
with good exercise capacity,150 and for those with
reduced exercise capacity.151 Table 2 summarizes major studies that reported the prognostic use of stress
echocardiography in patients with known or suspected CAD.152-154 Table 3 shows predictors of
outcome found in these and other studies. Stress
echocardiography has been shown to provide incremental prognostic value for predicting overall mortality, cardiac mortality, and composite cardiac end
points in patients with known or suspected CAD,
after adjustment for risk factors and stress test
parameters.
A normal exercise echocardiogram result is
associated with an annual event rate of cardiac
death and nonfatal myocardial infarction of
less than 1%, equivalent to that of an age- and
sex-matched population. These patients do not
require further diagnostic evaluation unless
there is a change in clinical status.155,156 Patients with a normal pharmacologic stress
echocardiogram result have a slightly higher
event rate.22 This may be explained by the
higher risk status of patients who are unable to
perform exercise stress test, as this group
tends to be older with more comorbidities.
Ischemia was shown in many studies to be associated with incremental risk of mortality and cardiac
events. Patients with extensive stress-induced
abnormalities in a multivessel distribution are
at a high risk of mortality and cardiac events. In
these patients, coronary angiography and subsequent myocardial revascularization may be justified,
with particular consideration of symptomatic status,
functional capacity, and resting LV function. An
exercise wall-motion score index greater than 1.4 or
exercise EF less than 50% portends a significantly
worse prognosis. Results of stress echocardiography
have been combined with the Duke treadmill score
and clinical and stress test variables including age,
sex, symptoms, exercise tolerance, rate-pressure
product, and severity of wall-motion abnormalities.157-159
Baseline LV function expressed as wall-motion
score index or EF remains a powerful predictor of
future events. Patients with resting LV dysfunction but no inducible myocardial ischemia
have an intermediate risk, whereas patients
with resting LV dysfunction and new wallmotion abnormalities have the greatest risk for
death and cardiac events.
Table 3 summarizes stress echocardiography test
results characterizing patients at increased risk. In
addition to baseline LV dysfunction, variables
associated with adverse outcome include extensive ischemia,65,160-162 poor EF response or
failure to reduce end-systolic volume with exercise,150 wall-motion abnormalities in mul-
Journal of the American Society of Echocardiography
Volume 20 Number 9
Pellikka et al 1031
Table 2 Summary of studies evaluating the value of stress echocardiography in predicting outcome
Author
No. of
patients
Arruda-Olson et al
2002161
Marwick et al
2001159
Biagini et al
2005162
Marwick et al
2001160
Chuah et al
199865
5798
Shaw et al 2005173
11,132
5375
3381
3156
860
Sicari et al
2003152
Tsutsui et al
2005153
7333
Bergeron et al
2004123
Elhendy et al
2001163
Sozzi et al
2003187
Marwick et al
2002188
Chaowalit et al
2006186
3260
788
Patient
characteristics
Stress type
Mean or
median
follow-up, y
End point
Echocardiographic
predictors
Known or
suspected CAD
Known or
suspected CAD
Known or
suspected CAD
Known or
suspected CAD
Known or
suspected CAD
Exercise
3.2
Cardiac death/MI
Exercise WMSI
Exercise
5.5
All deaths
Dobutamine
7
Cardiac death/MI
Extent of resting WMA;
extent of ischemia
Resting WMA, ischemia
Dobutamine
3.8
Cardiac death
Resting WMA, ischemia
Dobutamine
2
Cardiac death/MI
Known or
suspected CAD
Known or
suspected CAD
Known or
suspected CAD
Exercise or
dobutamine
Dipyridamole or
dobutamine
Dobutamine
myocardial
contrast
perfusion
Exercise
5
Cardiac death
2.6
Cardiac death/MI
1.7
Death/MI
Stress WMA; endsystolic volume
response
Extent of resting WMA;
extent of ischemia
Resting EF, change in
WMSI
Contrast perfusion
defects
3.1
Mortality/morbidity
Change in WMSI
Exercise
3
Cardiac death/MI
EF, extent of ischemia
563
Chest pain or
dyspnea
Diabetes
396
Diabetes
Dobutamine
3
Cardiac death/MI
EF, extent of ischemia
937
Diabetes
3.9
All deaths
2349
Diabetes
Exercise or
dobutamine
Dobutamine
5.4
Arruda et al
2001184
Biagini et al
2005185
Carlos et al
1997178
2632
Elderly (ⱖ65 y)
Exercise
2.9
Mortality/morbidity
(MI, late
coronary
revascularization)
Cardiac death/MI
Extent of resting WMA;
extent of ischemia
Extent of ischemia and
failure to reach target
heart rate
1434
Elderly (⬎65 y)
Dobutamine
6.5
Cardiac death/MI
214
Acute MI
Dobutamine
1.4
Resting WMSI; remote
abnormalities
Elhendy et al
2005183
Elhendy et al
2003154
528
Heart failure
Dobutamine
3.2
Cardiac death, MI,
arrhythmias,
heart failure
Cardiac death
483
3
Cardiac death/MI
Resting WMSI, EF
response
Arruda et al
2001198
Bountiouko et al
2004199
718
LVH by
Exercise
echocardiographic
criteria
Previous CABG
Exercise
2.9
Cardiac death/MI
331
Previous CABG
or PCI
Dobutamine
2
Biagini et al
200531
Das et al 200061
136
Pacing
3.5
Poldermans et al
1997193
360
Pacemaker
recipients
Before
nonvascular
surgery
Before vascular
surgery
Cardiac death/MI/
late
revascularization
Cardiac death
Changes of EF and endsystolic volume
Ischemia
Sicari et al
1999191
509
Before vascular
surgery
Dipyridamole
530
Dobutamine
Dobutamine
Hospital
stay
1.6
Hospital
stay
Changes of EF and endsystolic volume
Resting WMA, ischemia
Resting EF, ischemia
Ischemia
Cardiac death/MI
Ischemic threshold
Perioperative and
late cardiac
events
Death, MI,
unstable angina
Ischemia
Ischemia
CABG, Coronary artery bypass grafting; CAD, coronary artery disease; EF, ejection fraction; LVH, left ventricular hypertrophy; MI, myocardial infarction; PCI,
percutaneous intervention; WMA, wall-motion abnormalities; WMSI, wall-motion score index.
Journal of the American Society of Echocardiography
September 2007
1032 Pellikka et al
Table 3 Stress echocardiography predictors of risk
Very low risk* MI, cardiac events
< 1%/y
Low risk* MI, cardiac
death < 2%/y
Factors increasing risk†
™™™™™™™™™™™™™™™™™™™™™3
High risk‡ RR > 4-fold over
low risk
Normal exercise echocardiogram
result with good exercise capacity
7 METs men
5 METs women
Normal pharmacologic
stress echocardiogram
result with adequate
stress, defined as
achievement of HR ⱖ
85% age-predicted
maximum for
dobutamine stress, and
low to intermediate
pretest probability of
CAD
Increasing age
Male sex
Diabetes
High pretest probability
History of dyspnea or CHF
History of myocardial infarction
Limited exercise capacity
Inability to exercise
Stress ECG with ischemia
Rest WMA
LV hypertrophy
Stress echocardiography with
ischemia
Reduced baseline EF
No change or increase ESV
with stress§
No change or decrease EF
with stress§
Increasing wall-motion score
with stress
Extensive rest WMA (4-5
segments of LV)
Baseline EF ⬍ 40%
Extensive ischemia (4-5
segments of LV)
Multivessel ischemia
Rest WMA and remote
ischemia
Low ischemic threshold
Ischemia with 0.56 mg/kg
dipyridamole or 20 ␮g/
kg/min dobutamine or
based on heart rate//
Ischemic WMA, no change or
decrease in exercise EF§
CAD, Coronary artery disease; CHF, congestive heart failure; ECG, electrocardiogram; EF, ejection fraction; ESV, end-systolic volume; HR, heart rate; LV, left
ventricular; METs, metabolic equivalents; MI, myocardial infarction; WMA, wall-motion abnormalities.
*High pretest probability of CAD, poor exercise capacity or low rate-pressure product, increased age, angina during stress, LV hypertrophy, history of infarction,
history of CHF, and anti-ischemic therapy are factors known to increase risk in patients with normal stress echocardiogram results.
†The degree to which each factor increases risk is variable.
‡Cut-off values for high-risk group are approximate values derived from available studies. Studies have shown that increased rest and low- and peak-dose
wall-motion scores can identify individuals at high risk, especially those with reduced global LV function, but threshold values used to define patients at high risk
have been variable (eg, peak exercise scores range from 1.4 to ⬎ 1.7).
§For treadmill and dobutamine stress.
//Low ischemic threshold based on HR for dobutamine stress has been defined in various studies as ischemia with HR ⬍ 60% of age-predicted maximum, HR
⬍ 70% of age-predicted maximum, or at HR ⬍ 120/min.
tivessel distribution,163 a low ischemic threshold,61 LV hypertrophy,155 and location of wallmotion abnormalities in left anterior
descending coronary artery distribution.164 Akinesis becoming dyskinesis is associated with more
extensive LV dysfunction, absence of reversible
perfusion defects,165 and very low probability of
regional improvement after revascularization.166 In
the presence of concomitant anti-ischemic therapy,
a positive test result is more prognostically malignant, and a negative test result less prognostically
benign.167
The prognostic use of stress echocardiography
has been established in specific patient groups
including those with hypertension,168,169 electronic
pacemaker,31 left bundle branch block,170 LV dysfunction,171 and atrial fibrillation.172 Use in other
groups is described below.
Women
The prognostic value of stress echocardiography is well
established in both men and women.161,162,173-175
Although some studies have reported a higher incidence of cardiac events in men than in women after
a normal study, the magnitude of risk associated
with stress echocardiographic abnormalities is
independent of sex.161,162
After Acute Myocardial Infarction
Resting LV function is a major determinant of prognosis after myocardial infarction. Stress echocardiography can be performed safely early after myocardial infarction and provides not only assessment
of global and regional ventricular function, but
can detect the presence and extent of residual
myocardial ischemia.176 Several studies have confirmed that the extent of residual ischemia is related to
adverse cardiac outcomes in this setting and provides
information incremental to that obtained by exercise
ECG177 or angiography.178-181 The incremental prognostic value of stress echocardiography is preserved in
patients with abnormal LV function.182 In patients
with heart failure and low EF because of ischemic
cardiomyopathy, myocardial ischemia during dobutamine stress echocardiography was predictive of cardiac death, especially among patients who did not
undergo coronary revascularization.183
Journal of the American Society of Echocardiography
Volume 20 Number 9
Elderly
Exercise echocardiography has been demonstrated to be a useful noninvasive tool for the
evaluation of CAD in the elderly. The addition of
stress echocardiographic variables that reflect not
only the presence, but extent, of ischemia (in particular LV end-systolic volume response and exercise
EF) to clinical, exercise ECG data and resting echocardiographic data has improved the prediction of
cardiac events and all-cause mortality.184 Pharmacologic stress echocardiography can independently predict mortality among elderly patients unable to exercise.185 Patients with both
resting and stress-induced wall-motion abnormalities
were at highest risk of cardiac events.
Patients with Diabetes Mellitus
Exercise echocardiography is effective for cardiac risk stratification of patients with diabetes
mellitus. Approximately one of 3 patients with
multivessel distribution of exercise wall-motion abnormalities will experience cardiac death or myocardial infarction during the 3 years after the stress
test.163 Many patients with diabetes are unable to
undergo an exercise stress test because of the higher
prevalence of peripheral vascular disease and neuropathy. Such patients generally represent a higherrisk population than those who are able to undergo
exercise stress testing. Dobutamine stress echocardiography was shown to provide independent prognostic information.186-188
Before Noncardiac Surgery
Cardiac risk factors and stress tests help to identify
patients at high risk before major vascular surgery,
identifying those who will benefit from coronary revascularization or pharmacologic (beta-blocker) therapy.189 Pharmacologic stress echocardiography has
been shown to be a powerful tool for cardiac risk
stratification before vascular190-193 and nonvascular61
surgery. Test results provided better risk stratification
than that which can be gained from clinical indices.61
Extensive ischemia (ⱖ3-5 segments) has a strong independent prognostic impact and may identify patients
who would benefit most from revascularization before
noncardiac surgery. Ischemia occurring at less than
60% of age-predicted maximal heart rate identifies
patients at highest risk.61 In a recent meta-analysis
comparing 6 noninvasive techniques for preoperative
risk stratification before vascular surgery, pharmacologic stress tests had a higher overall sensitivity and
specificity than the other tests. For preoperative risk
stratification, dobutamine stress echocardiography had a similar sensitivity to myocardial perfusion scintigraphy and a higher specificity and a
better overall predictive accuracy.190,194 In patients at clinically intermediate and high risk receiving
beta-blockers, dobutamine stress echocardiography
Pellikka et al 1033
can help identify those in whom surgery can still be
performed and those in whom cardiac revascularization should be considered.189
After Coronary Revascularization
Stress echocardiography can localize restenosis or graft occlusion, detect native unrevascularized CAD, and assess adequacy of revascularization.194,196 Positive stress echocardiography
after coronary angioplasty identifies patients at high
risk for recurrence of angina.197 Ischemia by stress
echocardiography was incrementally predictive of
cardiac events.198,199 In patients with previous coronary artery bypass grafting, the addition of the
exercise echocardiographic variables, abnormal LV
end-systolic volume response and exercise EF, to the
clinical, resting echocardiographic, and exercise
ECG model provided incremental information in
predicting cardiac events.198 However, routine use
of stress testing in asymptomatic patients early after
revascularization is not indicated.
Patients with Angina
The specificity of the symptom, angina, for the detection of underlying CAD is limited. Inducible ischemia
during stress echocardiography was observed in only
approximately 50% of patients with angina. In patients
with stable angina, a normal stress echocardiogram
finding identifies patients at low risk of cardiac events.
In patients with CAD, angina is a poor predictor of the
amount of myocardial ischemia. In patients with
angina, stress echocardiography can provide objective evidence of myocardial ischemia and determine the extent of myocardium at risk200 and has
been shown to be useful for risk stratification.201
Comparison with Radionuclide Imaging
The annual cardiac event rate of less than 1%
after a normal stress echocardiogram result is
comparable with the event rate after a normal
stress radionuclide imaging result reported in
the current American Society of Nuclear Cardiology (ASNC)/ACC/AHA guidelines and in a recent
meta-analysis.202,203 Both wall-motion score index for stress echocardiography and summed
stress score used in radionuclide imaging have
been shown to be directly associated with the
incidence of cardiac events during follow-up.
Studies comparing stress echocardiography with
radionuclide imaging in the same population204,205 and several meta-analyses190,194,203
have demonstrated comparable prognostic use.
In a study of 301 patients who underwent simultaneous dobutamine stress echocardiography and sestamibi single photon emission computed tomography
(SPECT) radionuclide imaging and were followed up
for a mean of 7 years, the annual cardiac death rate was
0.7% after a normal SPECT result and 0.6% after a
1034 Pellikka et al
normal stress echocardiogram result. Abnormalities
with either technique were equally predictive of cardiac death and composite end points.206 The prognosis and cost-effectiveness of exercise echocardiography versus SPECT imaging were compared in large
numbers of stable patients at intermediate risk with
chest pain. The risk-adjusted 3-year death or myocardial infarction rates classified by extent of ischemia
were similar. A strategy based on cost-effectiveness
supported the use of echocardiography in patients at
low risk with suspected CAD and SPECT imaging in
those at higher risk.207 Advantages of stress echocardiography include shorter imaging time, lack
of ionizing radiation, portability, immediate
availability of the results, lower cost, and availability of ancillary information about chamber
sizes and function, valves, pericardial effusion,
aortic root disease, and wall thicknesses.
RECENT AND FUTURE DEVELOPMENTS
Strain and Strain Rate Echocardiography
As discussed, strain and strain rate imaging using
Doppler and 2D echocardiography-based techniques permit quantification of regional function
with stress.72-75 Further modifications in protocols
and software will enhance application of these
techniques to clinical practice.
Three-dimensional Echocardiography
Real-time 3-dimensional echocardiography using matrix-array transducers allows rapid acquisition of a
3-dimensional data set with stress. This data set can be
sliced to permit visualization of multiple 2D views of
the LV, allowing assessment of function in segments of
myocardium that are not routinely seen with 2D
scanners. The ability to obtain multiple 2D views
permits exact matching of baseline and stress views,
which may be important for detection of limited
wall-motion abnormalities. The feasibility of real-time
3-dimensional stress echocardiography has been documented.208-210 Continued improvements in image quality
will likely result in increased use of this method.
Myocardial Contrast Perfusion Imaging
The onset of ischemic wall-motion abnormalities is
preceded by development of regional disparities in
coronary perfusion that can be assessed by contrast
agents. Thus, use of contrast agents to assess myocardial perfusion during vasodilator stress may improve
the sensitivity of stress echocardiography.211 Both
real-time (low energy) and triggered (high energy)
imaging techniques have been shown to be useful for
detection of coronary stenosis. The timing of contrast
replenishment of a vascular bed has been found to be
a useful indicator of the degree of coronary stenosis.212
Journal of the American Society of Echocardiography
September 2007
Myocardial contrast perfusion imaging may have
greater sensitivity than wall-motion analysis.213,214
However, the specificity of contrast perfusion imaging
may be lower than for wall-motion analysis.
SUMMARY
Stress echocardiography is a well-validated tool for
detection and assessment of CAD. Its prognostic value
has been well documented in multiple large studies,
which have demonstrated its role for preoperative risk
stratification before noncardiac surgery, recovery of
function of viable myocardium, and identification of
patients at increased risk of cardiac events and death.
The test is less expensive than other stress imaging
modalities, providing accuracy for detection of CAD
and prognostic information equivalent to SPECT perfusion imaging. Moreover, it has great versatility, permitting assessment of valvular and pericardial abnormalities, chamber sizes, and wall thicknesses.
The authors appreciate the thoughtful review of this
manuscript by Harvey Feigenbaum, MD, Editor-in-Chief,
Journal of the American Society of Echocardiography.
REFERENCES
1. Armstrong W, Pellikka P, Ryan T, Crouse L, Zoghbi W, Stress
Echocardiography Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography.
Stress echocardiography: recommendations for performance
and interpretation of stress echocardiography. J Am Soc Echocardiogr 1998;11:97-104.
2. Feigenbaum H. Digital recording, display, and storage of
echocardiograms. J Am Soc Echocardiogr 1988;1:378-83.
3. Skolnick D, Sawada S, Feigenbaum H, Segar D. Enhanced
endocardial visualization with noncontrast harmonic imaging during stress echocardiography. J Am Soc Echocardiogr
1999;12:559-63.
4. Franke A, Hoffman R, Kuhl H. Non-contrast second harmonic imaging improves interobserver agreement and accuracy of dobutamine stress echocardiography in patients with
impaired image quality. Heart 2000;83:133-40.
5. Sozi F, Poldermans D, Bax J. Second harmonic imaging
improves sensitivity of dobutamine stress echocardiography
for the diagnosis of coronary artery disease. Am Heart J
2001;142:153-9.
6. Rainbird A, Mulvagh S, Oh J, McCully R, Klarich K, Shub C,
et al. Contrast dobutamine stress echocardiography: clinical
practice assessment in 300 consecutive patients. J Am Soc
Echocardiogr 2001;14:378-85.
7. Vlassak I, Rubin D, Odabashian J. Contrast and harmonic
imaging improves the accuracy and efficiency of novice readers for dobutamine stress echocardiography. Echocardiography 2002;19:483-8.
8. Dolan M, Riad K, El-Shafei A. Effect of intravenous contrast
for left ventricular opacification and border definition on
sensitivity and specificity of dobutamine stress echocardiography compared with coronary angiography in technically
difficult patients. Am Heart J 2001;142:908-15.
Journal of the American Society of Echocardiography
Volume 20 Number 9
9. Thanigaraji S, Nease R, Schechtman K, Wade R, Loslo S,
Perez J. Use of contrast for image enhancement during stress
echocardiography is cost-effective and reduces additional
diagnostic testing. Am J Cardiol 2001;87:1430-2.
10. Castello R, Bella J, Rovner A, Swan J, Smith J, Shaw J.
Efficacy and time-efficiency of “sonographer-driven” contrast echocardiography protocol in a high-volume echocardiography laboratory. Am Heart J 2003;145:535-41.
11. Bruce R, Kusumi F, Hosmer D. Maximal oxygen intake and
nomographic assessment of functional aerobic impairment in
cardiovascular disease. Am Heart J 1973;85:546-62.
12. Roger V, Pellikka P, Oh J, Miller FJ, Seward J, Tajik A. Stress
echocardiography, part I: exercise echocardiography; techniques, implementation, clinical applications, and correlations [see comments]. Mayo Clin Proc 1995;70:5-15.
13. Grunig E, Janssen B, Mereles D, Barth U, Borst M, Vogt I,
et al. Abnormal pulmonary artery pressure response in
asymptomatic carriers of primary pulmonary hypertension
gene. Circulation 2000;102:1145-50.
14. Modesto K, Rainbird A, Klarich K, Mahoney D, Chandrasekaran K, Pellikka P. Comparison of supine bicycle exercise and treadmill exercise Doppler echocardiography in
evaluation of patients with coronary artery disease. Am J
Cardiol 2003;91:1245-8.
15. Sawada S, Segar D, Ryan T, Brown S, Dohan A, Williams R,
et al. Echocardiographic detection of coronary artery disease
during dobutamine infusion. Circulation 1991;83:1605-14.
16. Mathias W Jr, Arruda A, Santos F, Arruda A, Mattos E,
Osorio A, et al. Safety of dobutamine-atropine stress echocardiography: a prospective experience of 4,033 consecutive
studies. J Am Soc Echocardiogr 1999;12:785-91.
17. Ling L, Pellikka P, Mahoney D, Oh J, McCully R, Roger V,
et al. Atropine augmentation in dobutamine stress echocardiography: role and incremental value in a clinical practice
setting. J Am Coll Cardiol 1996;28:551-7.
18. Lewandowski T, Armstrong W, Bach D. Reduced test time
by early identification of patients requiring atropine during
dobutamine stress echocardiography. J Am Soc Echocardiogr 1998;11:236-43.
19. Burger A, Notarianni M, Aronson D. Safety and efficacy of
an accelerated dobutamine stress echocardiography protocol
in the evaluation of coronary artery disease. Am J Cardiol
2000;86:825-9.
20. Pellikka P, Roger V, Oh J, Miller F Jr, Seward J, Tajik A.
Stress echocardiography, part II: dobutamine stress echocardiography; techniques, implementation, clinical applications,
and correlations [see comments]. Mayo Clin Proc 1995;70:
16-27.
21. Karagiannis S, Bax J, Elhendy A, Feringa H, Cookinos D, van
Domburg R, et al. Enhanced sensitivity of dobutamine stress
echocardiography by observing wall motion abnormalities
during the recovery phase after acute beta blocker administration. Am J Cardiol 2006;97:462-5.
22. Chaowalit N, McCully R, Callahan M, Mookadam F, Bailey
K, Pellikka P. Outcomes after normal dobutamine stress
echocardiography and predictors of adverse events: longterm follow-up of 3014 patients. Eur Heart J 2006;27:303944.
23. Cornel J, Balk A, Boersma E, Maat A, Elhendy A, Arnese M,
et al. Safety and feasibility of dobutamine-atropine stress
echocardiography in patients with ischemic left ventricular
dysfunction. J Am Soc Echocardiogr 1996;9:27-32.
24. Pellikka P, Roger V, Oh J, Seward J, Tajik A. Safety of
performing dobutamine stress echocardiography in patients
Pellikka et al 1035
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
with abdominal aortic aneurysm ⬎4 cm in diameter. Am J
Cardiol 1996;77:413-6.
Takhtehchian D, Novaro G, Barnett G, Griffin B, Pellikka P.
Safety of dobutamine stress echocardiography in patients
with unruptured intracranial aneurysms. J Am Soc Echocardiogr 2002;15:1401-4.
Elhendy A, Windle J, Porter T. Safety and feasibility of
dobutamine stress echocardiography in patients with implantable cardioverter defibrillators. Am J Cardiol 2003;92:
475-7.
Bremer M, Monahan K, Stussy V, Miller F Jr, Seward J,
Pellikka P. Safety of dobutamine stress echocardiography
supervised by registered nurse sonographers. J Am Soc Echocardiogr 1998;11:601-5.
Picano E, Lattanzi F. Dipyridamole echocardiography: a new
diagnostic window on coronary artery disease. Circulation
1991;83:III19-26.
Picano E, Marini C, Pirelli S, Maffei S, Bolognese L, Chiriatti
G, et al. Safety of intravenous high-dose dipyridamole echocardiography: the echo-Persantine international cooperative
study group. Am J Cardiol 1992;70:252-8.
Picano E, Alaimo A, Chubuchny V, Polonska E, Baldo V,
Baldini U, et al. Noninvasive pacemaker stress echocardiography for diagnosis of coronary artery disease: a multicenter
study. J Am Coll Cardiol 2002;40:1305-10.
Biagini E, Schinkel A, Elhendy A, Bax J, Rizzello V, van
Domburg R, et al. Pacemaker stress echocardiography predicts cardiac events in patients with permanent pacemaker.
Am J Med 2005;118:1381-6.
Lee C, Pellikka P, McCully R, Mahoney D, Seward J. Non
exercise stress transthoracic echocardiography: transesophageal atrial pacing versus dobutamine stress. J Am Coll Cardiol 1999;33:506-11.
Rainbird A, Pellikka P, Stussy V, Mahoney D, Seward J. A
rapid stress-testing protocol for the detection of coronary
artery disease: comparison of two-stage transesophageal
atrial pacing stress echocardiography with dobutamine stress
echocardiography. J Am Coll Cardiol 2000;36:1659-63.
Quinones M, Douglas P, Foster E, Gorcsan J, Lewis J,
Pearlman A, et al. ACC/AHA clinical competence statement
on echocardiography: a report of the American College of
Cardiology/American Heart Association/American College
of Physicians-American Society of Internal Medicine task
force on clinical competence. J Am Coll Cardiol 2003;41:
687-708.
Bierig S, Ehler D, Knoll M, Waggoner A. American Society
of Echocardiography minimum standards for the cardiac
sonographer: a position paper. J Am Soc Echocardiogr 2006;
19:471-4.
Lang R, Bierig M, Devereux R, Flachskampf F, Foster E,
Pellikka P, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s guidelines and standards committee and the chamber quantification writing group, developed in conjunction
with the European Association of Echocardiography, a
branch of the European Society of Cardiology. J Am Soc
Echocardiogr 2005;18:1440-63.
Senior R, Lahiri A. Enhanced detection of myocardial ischemia by stress dobutamine echocardiography utilizing the
“biphasic” response of wall thickening during low and high
dose dobutamine infusion. J Am Coll Cardiol 1995;26:2632.
Journal of the American Society of Echocardiography
September 2007
1036 Pellikka et al
38. Tyberg J, Parmley W, Sonnenblick E. In-vitro studies of
myocardial asynchrony and regional hypoxia. Circ Res 1969;
25:569-79.
39. Pislaru C, Belohlavek M, Bae R, Abraham T, Greenleaf F,
Seward J. Regional asynchrony during acute myocardial ischemia quantified by ultrasound strain rate imaging. J Am Coll
Cardiol 2001;37:1141-8.
40. Sutherland G, Kukulski T, Kvitting J, D’hooge J, Arnold M,
Brandt E. Quantitation of left-ventricular asynergy by cardiac
ultrasound. Am J Cardiol 2000;86:4-9G.
41. Kvitting J, Wigstrom L, Strotmann J, Sutherland G. How
accurate is visual assessment of synchronicity in myocardial
motion? An in vitro study with computer simulated regional
delay in myocardial motion: clinical implications for rest and
stress echocardiography studies. J Am Soc Echocardiogr
1999;12:698-705.
42. Hoffmann R, Marwick T, Poldermans D, Lethen H, Ciani R,
van der Meer P. Refinements in stress echocardiographic
techniques improve inter-institutional agreement in interpretation of dobutamine stress echocardiograms. Eur Heart J
2002;23:821-9.
43. Johnson L, Ellis K, Schmidt D, Weiss M, Cannon P. Volume
ejected in early systole: a sensitive index of left ventricular
performance in coronary artery disease. Circulation 1975;52:
1075-83.
44. Holman B, Wynne J, Idoine J, Neill J. Disruption in the
temporal sequence of regional ventricular contraction, I:
characteristics and incidence in coronary artery disease. Circulation 1980;61:1075-83.
45. Arsenault M, Crete M, Bergeron S. Left ventricular shape
assessment: a new simple diagnostic tool in stress echocardiography. J Am Soc Echocardiogr 2002;15:1321-5.
46. Attenhofer C, Pellikka P, Oh J, Roger V, Sohn D, Seward J.
Comparison of ischemic response during exercise and dobutamine echocardiography in patients with left main coronary
artery disease. J Am Coll Cardiol 1996;27:1171-7.
47. Roman S, Vilacosta J, Rollan M, Castillo J, Alonso J, Duran
J, et al. Right ventricular asynergy during dobutamine-atropine echocardiography. J Am Coll Cardiol 1997;30:430-5.
48. O’Sullivan C, Duncan A, Daly C, Li W, Oldershaw P,
Henein M. Dobutamine stress-induced ischemic right ventricular dysfunction and its relation to cardiac output in
patients with three-vessel coronary artery disease with angina-like symptoms. Am J Cardiol 2005;62:622-7.
49. Carstensen S, Ali S, Stensgaard-Hansen F, Toft J, Haunso S,
Kelbaek H. Dobutamine-atropine stress echocardiography in
asymptomatic healthy individuals: the relativity of stressinduced hyperkinesia. Circulation 1995;92:3453-63.
50. Coletta C, Galati A, Ricci R, Sestili A, Guagnozzi G, Re F, et
al. Prognostic value of left ventricular volume response during dobutamine stress echocardiography. Eur Heart J 1997;
18:1599-605.
51. Olson C, Porter T, Deligonul U, Xie F, Anderson J. Prognostic value of left ventricular volume response during dobutamine stress echocardiography. J Am Coll Cardiol 1994;
24:1268-73.
52. Anselmi M, Golia G, Marino P, Vitolo A, Rossi A, Caraffi G,
et al. Comparison of left ventricular function and volumes
during transesophageal atrial pacing combined with two
dimensional echocardiography in patients with syndrome X,
atherosclerotic coronary artery disease, and normal subjects.
Am J Cardiol 1997;80:1261-5.
53. Labovitz A, Pearson A, Chaitman B. Doppler and twodimensional echocardiographic assessment of left ventricular
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
function before and after intravenous dipyridamole stress
testing for detection of coronary artery disease. Am J Cardiol
1988;62:1180-5.
Sochor H, Pachinger O, Ogris E, Probst P, Kaindl F. Radionuclide imaging after coronary vasodilation: myocardial scintigraphy with thallium-201 and radionuclide angiography
after administration of dipyridamole. Eur Heart J 1984;5:
500-9.
Klein H, Ninio R, Eliyahu S, Bakst A, Levi A, Dean H.
Effects of the dipyridamole test on left ventricular function in
coronary artery disease. Am J Cardiol 1992;69:482-8.
Ginzton L, Conant R, Brizendine M, Lee F, Mena I, Laks M.
Exercise subcostal two-dimensional echocardiography: a
new method of segmental wall motion analysis. Am J Cardiol
1984;53:805-11.
Freeman M, Berman D, Staniloff H, Elkayam U, Maddahi J,
Swan H. Comparison of upright and supine bicycle exercise
in the detection and evaluation of extent of coronary artery
disease by equilibrium radionuclide ventriculography. Am
Heart J 1981;102:182-9.
Zwehl W, Gueret P, Meerbaum S, Holt D, Corday E.
Quantitative two dimensional echocardiography during bicycle exercise in normal subjects. Am J Cardiol 1981;47:86673.
Poliner L, Dehmer G, Lewis S, Parkey R, Blomqvist C,
Willerson J. Left ventricular performance in normal subjects:
a comparison of the responses to exercise in the upright and
supine positions. Circulation 1980;62:528-34.
Poldermans D, Arnese M, Fioretti P, Salustri A, Boersma E,
Thomson I, et al. Improved cardiac risk stratification in
major vascular surgery with dobutamine-atropine stress
echocardiography. J Am Coll Cardiol 1995;26:648-53.
Das M, Pellikka P, Mahoney D, Roger V, Oh J, McCully R,
et al. Assessment of cardiac risk before nonvascular surgery:
dobutamine stress echocardiography in 530 patients. J Am
Coll Cardiol 2000;35:1647-53.
Panza J, Curiel R, Laurienzo J, Quyyumi A, Dilsizian V.
Relation between ischemic threshold measured during dobutamine stress echocardiography and known indices of poor
prognosis in patients with coronary artery disease. Circulation 1995;92:2095-101.
Hoffmann R, Lethen H, Marwick T, Arnese M, Fioretti P,
Pingitore A, et al. Analysis of interinstitutional observer
agreement in interpretation of dobutamine stress echocardiograms. J Am Coll Cardiol 1996;27:330-6.
Anand D, Theodosiadis I, Senior R. Improved interpretation
of dobutamine stress echocardiography following 4 months
of systematic training in patients following acute myocardial
infarction. Eur J Echocardiogr 2004;5:12-7.
Chuah S, Pellikka P, Roger V, McCully R, Seward J. Role of
dobutamine stress echocardiography in predicting outcome
in 860 patients with known or suspected coronary artery
disease. Circulation 1998;97:1474-80.
Lang R, Vignon P, Weinert L, Bednarz J, Korcarz C, Sandelski J, et al. Echocardiographic quantification of regional left
ventricular wall motion with color kinesis. Circulation 1996;
93:1877-85.
Mor-Avi V, Vignon P, Koch R. Segmental analysis of color
kinesis images: new method for quantification of the magnitude and timing of endocardial motion during left ventricular
systole and diastole. Circulation 1997;95:2082-97.
Cain P, Baglin T, Case C, Spicer D, Short L, Marwick T.
Application of tissue Doppler to interpretation of dobut-
Journal of the American Society of Echocardiography
Volume 20 Number 9
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
amine echocardiography and comparison with quantitative
coronary angiography. Am Coll Cardiol 2001;87:525-31.
Madler C, Payne N, Wilkenshoff U. Non-invasive diagnosis
of coronary artery disease by quantitative stress echocardiography: optimal diagnostic models using off-line tissue Doppler in the MYDISE study. Eur Heart J 2003;24:1587-94.
Fathi R, Cain P, Nakatani S, Yu H, Marwick T. Effect of
tissue Doppler on the accuracy of novice and expert interpreters of dobutamine echocardiography. Am J Cardiol
2001;88:400-5.
Pislaru R, Bruce P, Anagnostopoulos L, Allen J, Seward C,
Pellikka J, et al. Ultrasound strain imaging of altered myocardial stiffness: stunned versus infarcted reperfused myocardium. Circulation 2004;109:2905-10.
Abraham T, Belohlavek M, Thomson H, Pislaru C, Khandheria B, Randolph G, et al. Time to onset of regional relaxation: feasibility, variability and utility of a novel index of
regional myocardial function by strain rate imaging. J Am
Coll Cardiol 2002;39:1531-7.
Voigt J, Nixdorff U, Bogdan R, Exner B, Schmiedehausen K,
Platsch G, et al. Comparison of deformation imaging and
velocity imaging for detecting regional inducible ischemia
during dobutamine stress echocardiography. Eur Heart J
2004;25:1517-25.
Merli E, Sutherland G. Can we quantify ischemia during
dobutamine stress echocardiography in clinical practice? Eur
Heart J 2004;25:1477-9.
Yip G, Khandheria B, Belohlavek M. Strain echocardiography tracks dobutamine-induced decrease in regional myocardial perfusion in nonocclusive coronary stenosis. J Am Coll
Cardiol 2004;44:1664-71.
Marwick T. Measurement of strain and strain rate by echocardiography: ready for prime time? J Am Coll Cardiol
2006;47:1313-27.
Quinones M, Verani M, Haichin R, Mahmarian J, Suarez J,
Zog W. Exercise echocardiography versus 201T1 singlephoton emission computed tomography in evaluation of
coronary artery disease: analysis of 292 patients. Circulation
1992;85:1217-8.
Fleischmann K, Hunink M, Kuntz K, Douglas P. Exercise
echocardiography or exercise SPECT imaging? A meta-analysis of diagnostic test performance. JAMA 1998;280:91320.
Schinkel A, Bax J, Geleijnse M, Boersma E, Elhendy A,
Roelandt J, et al. Noninvasive evaluation of ischemic heart
disease: myocardial perfusion imaging or stress echocardiography? Eur Heart J 2003;24:789-800.
Smart S, Bhatia A, Hellman R, Stoiber T, Krasnow A, Collier
D. Dobutamine-atropine stress echocardiography and dipyridamole sestamibi scintigraphy for the detection of coronary
artery disease: limitations and concordance. J Am Coll Cardiol 2000;36:1265-73.
Marwick T, D’Hondt A, Baudhuin T, Willemart B, Wijns W,
Detry J, et al. Optimal use of dobutamine stress for the
detection and evaluation of coronary artery disease: combination with echocardiography or scintigraphy, or both? J Am
Coll Cardiol 1993;22:159-67.
Roger VL, Pellikka PA, Bell MR, Chow CW, Bailey KR,
Seward JB. Sex and test verification bias: impact on the
diagnostic value of exercise echocardiography [see comments]. Circulation 1997;95:405-10.
McNeill A, Fioretti P, el-Said S, Salustri A, Forster T, Roelandt J. Enhanced sensitivity for detection of coronary artery
Pellikka et al 1037
84.
85.
86.
87.
88.
89.
90.
91.
92.
93.
94.
95.
96.
97.
98.
disease by addition of atropine to dobutamine stress
echocardiography. Am J Cardiol 1992;70:41-6.
Schroder K, Voller H, Dingerkus H, Munzberg H, Dissman
R, Linderer T. Comparison of the diagnostic potential of
four echocardiographic stress tests shortly after acute myocardial infarction: submaximal exercise, transesophageal
atrial pacing, dipyridamole, and dobutamine-atropine. Am J
Cardiol 1996;77:909-14.
Dagianti A, Penco M, Bandiera A, Sgorbini L, Fedele F.
Clinical application of exercise stress echocardiography: supine bicycle or treadmill? Am J Cardiol 1998;81:62-7G.
Badruddin S, Ahmad A, Mickelson J, et al. Supine bicycle
versus post-treadmill exercise echocardiography in the detection of myocardial ischemia: a randomized single-blind crossover trial. J Am Coll Cardiol 1999;33:1485-90.
Ryan T, Segar D, Sawada S, et al. Detection of coronary
artery disease with upright bicycle exercise echocardiography. J Am Soc Echocardiog 1993;6:186-97.
Hecht H, DeBord L, Shaw R, Dunlap R, Ryan C, Stertzer S,
et al. Usefulness of supine bicycle stress echocardiography for
detection of restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol 1993;71:293-6.
Hecht H, DeBord L, Sotomayor N, Shaw R, Dunlap R, Ryan
C. Supine bicycle stress echocardiography: peak exercise
imaging is superior to postexercise imaging. J Am Soc Echocardiogr 1993;6:265-71.
Smart S, Knickelbine T, Malik F, Sagar K. Dobutamineatropine stress echocardiography for the detection of coronary artery disease in patients with left ventricular hypertrophy: importance of chamber size and systolic wall stress.
Circulation 2000;101:258-63.
Yuda S, Khoury V, Marwick T. Influence of wall stress and
left ventricular geometry on the accuracy of dobutamine
stress echocardiography. J Am Coll Cardiol 2002;40:
1311-9.
Wahi S, Marwick T. Aortic regurgitation reduces the accuracy of exercise echocardiography for diagnosis of coronary
artery disease. J Am Soc Echocardiogr 1999;12:967-73.
Bach D, Muller D, Gros B, Armstrong W. False positive
dobutamine stress echocardiograms: characterization of clinical, echocardiographic and angiographic findings. J Am Coll
Cardiol 1994;24:928-33.
Ha J, Juracan E, Mahoney D, Oh J, Shub C, Seward J, et al.
Hypertensive response to exercise: a potential cause for new
wall motion abnormality in the absence of coronary artery
disease. J Am Coll Cardiol 2002;39:323-7.
Okeie K, Shimizu M, Yoshio H, Ino H, Yamaguchi M,
Matsuyama T, et al. Left ventricular systolic dysfunction
during exercise and dobutamine stress in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol 2000;36:
856-63.
Miller D, Ruddy T, Zusman R, Okada R, Strauss H, Kanarek
D. Left ventricular ejection fraction response during exercise
in asymptomatic systemic hypertension. Am J Cardiol 1987;
59:409-13.
Schulman D, Tugoen J, Flores A, Dianzumba S, Reichek N.
Left ventricular ejection fraction during supine and upright
exercise in patients with systemic hypertension and its relation to peak filling rate. Am J Cardiol 1995;76:61-5.
Melin J, Wijns W, Pouleur H, Robert A, Nannan M, DeCoster P, et al. Ejection fraction response to upright exercise
in hypertension: relation to loading conditions and to contractility. Int J Cardiol 1987;17:37-49.
1038 Pellikka et al
99. Mottram P, Haluska B, Yuda S, Leano R, Marwick T. Patients with a hypertensive response to exercise have impaired
systolic function without diastolic dysfunction or left ventricular hypertrophy. J Am Coll Cardiol 2004;43:848-53.
100. Mairesse G, Marwick T, Arnese M, Vanoverschelde J, Cornel
J, Detry J. Improved identification of coronary artery disease
in patients with left bundle branch block by use of dobutamine stress echocardiography and comparison with myocardial perfusion tomography. Am J Cardiol 1995;76:321-5.
101. Tandogan I, Yetkin E, Yanik A, Ulusoy F, Temizhan A,
Cehreli S. Comparison of thallium 201 exercise SPECT and
dobutamine stress echocardiography for diagnosis of coronary artery disease in patients with left bundle branch block.
Int J Cardiovasc Imaging 2001;17:339-45.
102. Geleijnse M, Vigna C, Kasprzak J, Rambaldi R, Salvatori M,
Elhendy A, et al. Usefulness and limitations of dobutamineatropine stress echocardiography for the diagnosis of coronary artery disease in patients with left bundle branch block.
Eur Heart J 2000;21:1666-73.
103. Afridi I, Grayburn P, Panza J, Oh J, Zoghbi W. Myocardial
viability during dobutamine echocardiography predicts survival in patients with coronary artery disease and severe left
ventricular systolic dysfunction. J Am Coll Cardiol 1998;32:
921-6.
104. Meluzin J, Cerny J, Frelich M, Stetka F, Spinarova L, Popelova J, et al. Prognostic value of the amount of dysfunctional
but viable myocardium in revascularized patients with coronary artery disease and left ventricular dysfunction: investigators of this multicenter study. J Am Coll Cardiol 1998;32:
912-20.
105. Naqvi T, Goel R, Forrester J, Siegel R. Myocardial contractile reserve on dobutamine echocardiography predicts late
spontaneous improvement in cardiac function in patients
with recent onset idiopathic dilated cardiomyopathy. J Am
Coll Cardiol 1999;34:1537-44.
106. Eichhorn E, Grayburn P, Mayer S, St John Sutton M,
Appleton C, Plehn J, et al. Myocardial contractile reserve by
dobutamine stress echocardiography predicts improvement
in ejection fraction with beta-blockade in patients with heart
failure: the beta-blocker evaluation of survival trial (BEST).
Circulation 2003;108:2336-41.
107. Nagueh S, Mikati I, Weilbaecher D, Reardon M, Al-Zaghrini
G, Cacela D, et al. Relation of the contractile reserve of
hibernating myocardium to myocardial structure in humans.
Circulation 1999;100:490-6.
108. Elsasser A, Schlepper M, Klovekorn W, Cai W, Zimmerman
R. Hibernating myocardium: an incomplete adaptation to
ischemia. Circulation 1997;96:2920-31.
109. Bito V, Heinzel F, Weidemann. Cellular mechanisms of
contractile dysfunction in hibernating myocardium. Circ Res
2004;94:794-801.
110. Iyer V, Canty J. Regional desensitization of beta-adrenergic
receptor signaling in swine with chronic hibernating myocardium. Circ Res 2005;97:789-95.
111. Schwarz E, Schoendube F, Schmiedtke S, Schultz G, Buell
U. Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after
revascularization. J Am Coll Cardiol 1998;31:1018-26.
112. Cwajg J, Cwajg E, Nagueh D, He Z, Qureshi U, Olmos L.
End-diastolic wall thickness as a predictor of recovery of
function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol 2000;35:1152-61.
Journal of the American Society of Echocardiography
September 2007
113. Biagini E, Galema T, Schinkel A, Vletter W, Roelandt J, Ten
Cate F. Myocardial wall thickness predicts recovery of contractile function after primary coronary intervention for
acute myocardial infarction. J Am Coll Cardiol 2004;43:
1489-93.
114. Yong Y, Nagueh S, Shimoni S, Shan K, He Z, Reardon M.
Deceleration time in ischemic cardiomyopathy: relation to
echocardiographic and scintigraphic indices of myocardial
viability and functional recovery after revascularization. Circulation 2001;103:1232-7.
115. Ling L, Christian T, Mulvagh S, Klarich K, Hauser M,
Nishimura R, et al. Determining myocardial viability in
chronic ischemic left ventricular dysfunction: a prospective
comparison of rest-redistribution thallium 201 single-photon emission computed tomography, nitroglycerin-dobutamine echocardiography, and intracoronary myocardial
contrast echocardiography. Am Heart J 2006;151:882-9.
116. Senior R, Lahiri A. Role of dobutamine echocardiography in
detection of myocardial viability for predicting outcome after
revascularization in ischemic cardiomyopathy. J Am Soc
Echocardiogr 2001;14:240-8.
117. Afridi I, Kleiman N, Raizner A, Zoghbi W. Dobutamine
echocardiography in myocardial hibernation: optimal dose
and accuracy in predicting recovery of ventricular function
after coronary angioplasty. Circulation 1995;91.
118. Bax J, Poldermans D, Elhendy A. Improvement of left
ventricular ejection fraction, heart failure symptoms and
prognosis after revascularization in patients with chronic
coronary artery disease and viable myocardium detected by
dobutamine stress echocardiography. J Am Coll Cardiol
1999;34:163-9.
119. Rizzello V, Poldermans D, Boersma E. Opposite patterns of
left ventricular remodeling after coronary revascularization
in patients with ischemic cardiomyopathy: role of myocardial
viability. Circulation 2004;110:2383-8.
120. Hoffmann R, Altiok E, Nowak B, Heussen N, Kuhl H,
Kaiser H, et al. Strain rate measurement by Doppler echocardiography allows improved assessment of myocardial viability in patients with depressed left ventricular function.
J Am Coll Cardiol 2002;39:443-9.
121. Hoffmann R, Altiok E, Nowak B, Kuhl H, Kaiser H, Buell U,
et al. Strain rate analysis allows detection of differences in
diastolic function between viable and nonviable myocardial
segments. J Am Soc Echocardiogr 2005;18:330-5.
122. Zhang Y, Chan A, Yu C, Yip G, Fung J, Lam W, et al. Strain
rate imaging differentiates transmural from non-transmural
myocardial infarction: a validation study using delayed-enhancement magnetic resonance imaging. J Am Coll Cardiol
2005;46:864-71.
123. Bergeron S, Ommen S, Bailey K, Oh J, McCully R, Pellikka
P. Exercise echocardiographic findings and outcome of patients referred for evaluation of dyspnea. J Am Coll Cardiol
2004;43:2242-6.
124. Ha J, Lulic F, Bailey K, Pellikka P, Seward J, Tajik A, et al.
Effects of treadmill exercise on mitral inflow and annular
velocities in healthy adults. Am J Cardiol 2003;91:114-5.
125. Ha J, Pellikka P, Oh J, Ommen S, Stussy V, Bailey K, et al.
Diastolic stress echocardiography: a novel noninvasive diagnostic test for diastolic dysfunction using supine bicycle
exercise Doppler echocardiography. J Am Soc Echocardiogr
2005;18:63-8.
126. Burgess M, Jenkins C, Sharman J, Marwick T. Diastolic
stress echocardiography: hemodynamic validation and clini-
Journal of the American Society of Echocardiography
Volume 20 Number 9
127.
128.
129.
130.
131.
132.
133.
134.
135.
136.
137.
138.
139.
cal significance of estimation of ventricular filling pressure
with exercise. J Am Coll Cardiol 2006;47:1891-900.
Galie N, Torbicki A, Barst R, Dartevelle P, Haworth S,
Higenbottam T, et al. Guidelines on diagnosis and treatment
of pulmonary arterial hypertension: the task force on diagnosis and treatment of pulmonary arterial hypertension of
the European Society of Cardiology. Eur Heart J 2004;25:
2243-78.
Himelman R, Stulbarg M, Kircher B, Lee E, Kee L, Dean N,
et al. Noninvasive evaluation of pulmonary artery pressure
during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease. Circulation 1989;79:86371.
Nootens M, Wolfkiel C, Chomka E, Rich S. Understanding
right and left ventricular systolic function and interactions at
rest and with exercise in primary pulmonary hypertension.
Am J Cardiol 1995;75:374-7.
Holverda S, Gan C, Marcus J, Postmus P, Boonstra A,
Vonk-Noordegraaf A. Impaired stroke volume response to
exercise in pulmonary arterial hypertension. J Am Coll Cardiol 2006;47:1732-3.
Bossone E, Rubenfire M, Bach D, Ricciardi M, Armstrong
W. Range of tricuspid regurgitation velocity at rest and
during exercise in normal adult men: implications for the
diagnosis of pulmonary hypertension. J Am Coll Cardiol
1999;33:1662-6.
Grunig E, Mereles D, Hildebrandt W, Swenson E, Kubler
W, Kuecherer H, et al. Stress Doppler echocardiography for
identification of susceptibility to high altitude pulmonary
edema. J Am Coll Cardiol 2000;35:980-7.
Wu W, Aziz G, Sadaniantz A. The use of stress echocardiography in the assessment of mitral valvular disease. Echocardiography 2004;21:451-8.
Bonow R, Carabello B, Chatterjee K, de Leon A, Faxon D,
Freed M, et al. ACC/AHA guidelines for the management
of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association
task force on practice guidelines (writing committee to revise
the 1998 guidelines for the management of patients with
valvular heart disease) developed in collaboration with the
Society of Cardiovascular Anesthesiologist endorsed by the
Society for Cardiovascular Angiography and Interventions
and the Society of Thoracic Surgeons. J Am Coll Cardiol
2006;48:e1-148.
Voelker W, Jaksch R, Dittman H, Schmitt A, Maiuser M,
Karsch K. Validation of continuous-wave Doppler measurement of mitral valve gradients during exercise: a simultaneous Doppler-catheter study. Eur Heart J 1989;10:737-46.
Aviles R, Nishimura R, Pellikka P, Andreen K, Holmes D.
Utility of stress Doppler echocardiography in patients undergoing percutaneous mitral balloon valve valvotomy. J Am
Soc Echocardiogr 2001;14:676-81.
Hecker S, Zabalgoitia M, Ashline P, Oneschuk L, O’Rourke
R, Herrera C. Comparison of exercise and dobutamine stress
echocardiography in assessing mitral stenosis. Am J Cardiol
1997;80:1374-7.
Mohan J, Patel A, Passey R, Gupta D, Kumar M, Arora R, et
al. Is the mitral valve area flow-dependent in mitral stenosis?
A dobutamine stress echocardiographic study. J Am Coll
Cardiol 2002;40:1809-15.
Zoghbi W, Enriquez-Sarano M, Foster E, Grayburn P, Kraft
C, Levine R, et al. American Society of Echocardiography:
recommendations for evaluation of the severity of native
valvular regurgitation with two-dimensional and Doppler
Pellikka et al 1039
140.
141.
142.
143.
144.
145.
146.
147.
148.
149.
150.
151.
152.
153.
echocardiography. J Am Soc Echocardiogr 2003;16:
777-802.
Tischler M, Battle R, Saha M, Niggel J, LeWinter M. Observations suggesting a high incidence of exercise-induced severe
mitral regurgitation in patients with mild rheumatic mitral valve
disease at rest. J Am Coll Cardiol 1995;25:128-33.
Pierard L, Lancellotti P. The role of ischemic mitral regurgitation in the pathogenesis of acute pulmonary edema.
N Engl J Med 2004;351:1627-34.
Leung D, Griffin B, Stewart W, Cosgrove D, Thomas J,
Marwick T. Left ventricular function after valve repair for
chronic mitral regurgitation: predictive value of preoperative
assessment of contractile reserve by exercise echocardiography. J Am Coll Cardiol 1996;28:1198-205.
deFilippi C, Willett D, Brickner M, Appleton C, Yancy C,
Eichhorn E, et al. Usefulness of dobutamine echocardiography
in distinguishing severe from nonsevere valvular aortic stenosis
in patients with depressed left ventricular function and low
transvalvular gradients. Am J Cardiol 1995;75:191-4.
Nishimura R, Grantham J, Connolly H, Schaff H, Higano S,
Holmes D. Low-output, low-gradient aortic stenosis in patients with depressed left ventricular systolic function: the
clinical utility of the dobutamine challenge in the catheterization laboratory. Circulation 2002;106:809-13.
Blais C, Burwash I, Mundigler G, Dumesnil J, Loho N,
Rader F, et al. Projected valve area at normal flow rate
improves the assessment of stenosis severity in patients with
low-flow, low-gradient aortic stenosis: the multicenter
TOPAS (truly or pseudo-severe aortic stenosis) study. Circulation 2006;113:711-21.
Monin J, Quere J, Monchi M, Petit H, Baleynaud S, Chauvel
C, et al. Low-gradient aortic stenosis; operative risk stratification and predictors for long-term outcome: a multicenter
study using dobutamine stress hemodynamics. Circulation
2003;108:319-24.
Zabalgoitia M, Kopec K, Abochamh D, Oneschuk L, Herrera
C, O’Rourke R. Usefulness of dobutamine echocardiography
in the hemodynamic assessment of mechanical prostheses in the
aortic valve position. Am J Cardiol 1997;80:523-6.
Izzat M, Birdi I, Wilde P, Bryan A, Angelini G. Evaluation of
the hemodynamic performance of small CarboMedics aortic
prostheses using dobutamine-stress Doppler echocardiography. Ann Thorac Surg 1995;60:104-52.
Zabalgoitia M, Kopec K, Oneschuk L, Linn W, Herrera C,
O’Rourke R. Use of dobutamine stress echocardiography in
assessing mechanical aortic prostheses: comparison with exercise echocardiography. J Heart Valve Dis 1997;6:253-7.
McCully R, Roger V, Mahoney D, Burger K, Click R, Seward J,
et al. Outcome after abnormal exercise echocardiography for
patients with good exercise capacity: prognostic importance of
the extent and severity of exercise-related left ventricular dysfunction. J Am Coll Cardiol 2002;39:1345-52.
McCully R, Roger V, Ommen S, Mahoney D, Burger K,
Freeman W, et al. Outcomes of patients with reduced exercise capacity at time of exercise echocardiography. Mayo Clin
Proc 2004;79:750-7.
Sicari R, Pasanisi E, Venneri L, Landi P, Cortigiani L, Picano
E. Stress echo results predict mortality: a large-scale multicenter prospective international study. J Am Coll Cardiol
2003;41:589-95.
Tsutsui J, Elhendy A, Anderson J, Zie F, McGrain A, Porter T.
Prognostic value of dobutamine stress myocardial contrast perfusion echocardiography. Circulation 2005;112:1440-50.
Journal of the American Society of Echocardiography
September 2007
1040 Pellikka et al
154. Elhendy A, Modesto K, Mahoney D, Khandheria B, Seward
J, Pellikka P. Prediction of mortality in patients with left
ventricular hypertrophy by clinical, exercise stress, and echocardiographic data. J Am Coll Cardiol 2003;41:129-35.
155. McCully R, Roger V, Mahoney D, Karon B, Oh J, Miller FJ,
et al. Outcome after normal exercise echocardiography and
predictors of subsequent cardiac events: follow-up of 1,325
patients. J Am Coll Cardiol 1998;31:144-9.
156. Sawada S, Ryan T, Conley M, Corya B. Prognostic value of a
normal exercise echocardiogram. Am Heart J 1990;120:49-55.
157. Elhendy A, Mahoney D, McCully R, Seward J, Burger K,
Pellikka P. Use of scoring model combing clinical, exercise
test, and echocardiographic data to predict mortality in
patients with known or suspected coronary artery disease.
Am J Cardiol 2004;93:1223-8.
158. Marwick T, Case C, Poldermans D, Boersma E, Bax J,
Sawada S, et al. A clinical and echocardiographic score for
assigning risk of major events after dobutamine echocardiograms. J Am Coll Cardiol 2004;43:2102-7.
159. Marwick T, Case C, Vasey C, Allen S, Short L, Thomas J.
Prediction of mortality by exercise echocardiography: a strategy for combination with the Duke treadmill score. Circulation 2001;103:2566-71.
160. Marwick T, Case C, Sawada S. Prediction of mortality using
dobutamine echocardiography. J Am Coll Cardiol 2001;37:
754-60.
161. Arruda-Olson A, Juracan E, Mahoney D, McCully R, Roger
V, Pellikka P. Prognostic value of exercise echocardiography
in 5,798 patients: is there a gender difference? J Am Coll
Cardiol 2002;39:625-31.
162. Biagini E, Elhendy A, Bax J, Rizzello V, Schinkel A, van
Domburg R, et al. Seven-year follow-up after dobutamine
stress echocardiography: impact of gender on prognosis.
J Am Coll Cardiol 2005;45:93-7.
163. Elhendy A, Arruda A, Mahoney D, Pellikka P. Prognostic
stratification of diabetic patients by exercise echocardiography. J Am Coll Cardiol 2001;37:1551-7.
164. Elhendy A, Mahoney D, Khandheria B, Paterick T, Burger
K, Pellikka P. Prognostic significance of the location of wall
motion abnormalities during exercise echocardiography.
J Am Coll Cardiol 2002;40:1623-9.
165. Elhendy A, Cornel J, Roelandt J, van Domburg R, Nierop P,
Geleynse MS, et al. Relation between contractile response of
akinetic segments during dobutamine stress echocardiography and myocardial ischemia assessed by simultaneous thallium-201 single-photon emission computed tomography.
Am J Cardiol 1996;77:955-9.
166. Elhendy A, Cornel J, Roelandt J, Van Domburg R, Fioretti
P. Akinesis becoming dyskinesis during dobutamine stress
echocardiography: a predictor of poor functional recovery
after surgical revascularization. Chest 1996;110:155-8.
167. Sicari R, Cortigiani L, Bigi R, Landi P, Raciti M, Picano E, et
al. Prognostic value of pharmacological stress echocardiography is affected by concomitant antiischemic therapy at the
time of testing. Circulation 2004;109:2428-31.
168. Marwick T, Case C, Sawada S, Vasey C, Thomas J. Prediction of outcomes in hypertensive patients with suspected
coronary disease. Hypertension 2002;39:1113-8.
169. Cortigiani L, Coletta C, Bigi R. Clinical, exercise electrocardiographic, and pharmacologic stress echocardiographic
findings for risk stratification of hypertensive patients with
chest pain. Am J Cardiol 2003;91:941-5.
170. Cortigiani L, Picano E, Vigna C, Lattanzi F, Coletta C,
Mariotti E, et al. Prognostic value of pharmacologic stress
171.
172.
173.
174.
175.
176.
177.
178.
179.
180.
181.
182.
183.
184.
185.
echocardiography in patients with left bundle branch block.
Am J Med 2001;110:361-9.
Smart S, Dionisopoulos P, Knickelbine T. Dobutamineatropine stress echocardiography for risk stratification in
patients with chronic left ventricular dysfunction. J Am Coll
Cardiol 1999;33:512-21.
Poldermans D, Bax J, Elhendy A, Sozzi F, Boersma E,
Thomson I, et al. Long-term prognostic value of dobutamine stress echocardiography in patients with atrial fibrillation. Chest 2001;119:144-9.
Shaw L, Vasey C, Sawada S, Rimmerman C, Marwick T.
Impact of gender on risk stratification by exercise and dobutamine stress echocardiography: long-term mortality in 4234
women and 6898 men. Eur Heart J 2005;26:447-56.
Marwick T, Anderson T, Williams M, Haluska B, Melin J,
Pashkow F, et al. Exercise echocardiography is an accurate
and cost-efficient technique for detection of coronary artery
disease in women. J Am Coll Cardiol 1995;26:335-41.
Elhendy A, Geleijnse M, van Domburg R. Gender differences in the accuracy of dobutamine stress echocardiography
for the diagnosis of coronary artery disease. Am J Cardiol
1997;80:1414-8.
Smart S, Knickelbine T, Stoiber T, Carlos M, Wynsen J, Sagar K.
Safety and accuracy of dobutamine-atropine stress echocardiography for the detection of residual stenosis of the infarct-related artery
and multivessel disease during the first week after acute myocardial
infarction. Circulation 1997;95:1394-401.
Desideri A, Fioretti P, Cortigiani L, Trocino G, Astarita C, Gregori
D, et al. Pre-discharge stress echocardiography and exercise ECG
for risk stratification after uncomplicated acute myocardial infarction: results of the COSTAMI-II (cost of strategies after myocardial infarction) trial. Heart 2005;91:146-51.
Carlos M, Smart S, Wynsen J, Sagar K. Dobutamine stress
echocardiography for risk stratification after myocardial infarction. Circulation 1997;95:1402-10.
Sicari R, Landi P, Picano E, Pirelli S, Chiaranda G, Previtali
M, et al. Exercise-electrocardiography and/or pharmacological stress echocardiography for non-invasive risk stratification early after uncomplicated myocardial infarction: a prospective international large scale multicenter study. Eur
Heart J 2002;23:1030-7.
Greco C, Salustri A, Seccareccia F, Ciavatti M, Biferali F,
Valtorta C, et al. Prognostic value of dobutamine echocardiography early after uncomplicated acute myocardial infarction: a comparison with exercise echocardiography. J Am
Coll Cardiol 1997;29:261-7.
Ryan T, Armstrong W, O’Donnell J, Feigenbaum H. Risk
stratification after acute myocardial infarction by means of
exercise two-dimensional echocardiography. Am Heart J
1987;114:1305-15.
Williams M, Obadashian J, Lauer M. Prognostic value of
dobutamine echocardiography in patients with left ventricular dysfunction. J Am Coll Cardiol 1996;27:132-9.
Elhendy A, Sozzi F, van Domburg R, Bax J, Schinkel A,
Roelandt J, et al. Effect of myocardial ischemia during dobutamine stress echocardiography on cardiac mortality in
patients with heart failure secondary to ischemic cardiomyopathy. Am J Cardiol 2005;96:469-73.
Arruda A, Das F, Roger R, Klarich J, Mahoney A, Pellikka
JPrognostic value of exercise echocardiography in 2,632 patients ⱖ 65 years of age. J Am Coll Cardiol 2001;37:1036-41.
Biagini E, Elhendy A, Schinkel A, Rizzello V, Bax J, Sozzi F,
et al. Long-term prediction of mortality in elderly persons by
Journal of the American Society of Echocardiography
Volume 20 Number 9
186.
187.
188.
189.
190.
191.
192.
193.
194.
195.
196.
197.
198.
199.
200.
201.
dobutamine stress echocardiography. J Gerontol A Biol Sci
Med Sci 2005;60:1333-8.
Chaowalit N, Arruda A, McCully R, Bailey K, Pellikka P.
Dobutamine stress echocardiography in patients with diabetes mellitus: enhanced prognostic prediction using a simple
risk score. J Am Coll Cardiol 2006;47:1029-36.
Sozzi F, Elhendy A, Roelandt J. Prognostic value of dobutamine stress echocardiography in patients with diabetes.
Diabetes Care 2003;26:1074-8.
Marwick T, Case C, Sawada S, Vasey C, Short L, Lauer M.
Use of stress echocardiography to predict mortality in patients with diabetes and known or suspected coronary artery
disease. Diabetes Care 2002;25:1042-8.
Boersma E, Poldermans D, Bax J, Steyerberg E, Thomson I,
Banga J, et al. Predictors of cardiac events after major vascular surgery: role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. J Am Med Assoc
2001;285:1865-73.
Shaw L, Eagle K, Gersh B, Miller D. Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994)
and dobutamine echocardiography (1991 to 1994) for risk
stratification before vascular surgery. J Am Coll Cardiol
1996;27:787-98.
Sicari R, Ripoli A, Picano E, Djordjevic-Dikic A, Di Giovanbattista
R, Minardi G, et al. Perioperative prognostic value of dipyridamole
echocardiography in vascular surgery: a large-scale multicenter
study in 509 patients; EPIC (echo Persantine international cooperative) study group. Circulation 1999;100:269-74.
Poldermans D, Fioretti P, Forster T, Thomson I. Dobutamine stress echocardiography for assessment of perioperative cardiac risk in patients undergoing major vascular surgery. Circulation 1993;87:1506-12.
Poldermans D, Arnese M, Fioretti P, Boersma E, Thomson I,
Rambaldi R, et al. Sustained prognostic value of dobutamine
stress echocardiography for late cardiac events after major noncardiac vascular surgery. Circulation 1997;95:53-8.
Kertai M, Boersma E, Bax J. A meta-analysis comparing the
prognostic accuracy of six diagnostic rests for predicting
perioperative cardiac risk in patients undergoing major vascular surgery. Heart 2003;89:1327-34.
Elhendy A, Geleijnse M, Roelandt J, Cornel J, van Domburg R, El-Rafaee M, et al. Assessment of patients after
coronary artery bypass grafting by dobutamine stress
echocardiography. Am J Cardiol 1996;77:1234-6.
Kafka H, Leach A, Fitzgibbon G. Exercise echocardiography
after coronary artery bypass surgery: correlation with coronary angiography. J Am Coll Cardiol 1995;25:1019-23.
Dagianti A, Rosanio S, Penco M, Dagianti A, Sciomer S,
Tocchi M, et al. Clinical and prognostic usefulness of supine
bicycle exercise echocardiography in the functional evaluation of patients undergoing elective percutaneous transluminal coronary angioplasty. Circulation 1997;95:1176-84.
Arruda A, McCully R, Oh J, Mahoney D, Seward J, Pellikka P.
Prognostic value of exercise echocardiography in patients after
coronary artery bypass surgery. Am J Cardiol 2001;87:1069-73.
Bountioukos M, Elhendy A, van Domburg R, Schinkel A,
Bax J, Krenning B, et al. Prognostic value of dobutamine
stress echocardiography in patients with previous coronary
revascularization. Heart 2004;90:1031-5.
Elhendy A, Mahoney D, Burger K, McCully R, Pellikka P.
Prognostic value of exercise echocardiography in patients
with classic angina pectoris. Am J Cardiol 2004;94:559-63.
Biagini E, Elhendy A, Schinkel A, Bax J, Vittoria R, van Domburg
R, et al. Risk stratification of patients with classic angina pectoris
Pellikka et al 1041
202.
203.
204.
205.
206.
207.
208.
209.
210.
211.
212.
213.
214.
and no history of coronary artery disease by dobutamine stress
echocardiography. J Am Coll Cardiol 2005;46:730-2.
Klocke F, Baird M, Lorell B, Bateman T, Messer J, Berman D, et
al. ACC/AHA/ASNC guidelines for the clinical use of cardiac
radionuclide imaging–executive summary: a report of the American College of Cardiology/American Heart Association task force
on practice guidelines (ACC/AHA/ASNC committee to revise
the 1995 guidelines for the clinical use of cardiac radionuclide
imaging). J Am Coll Cardiol 2003;42:1318-33.
Metz L, Beattie M, Hom R, Redberg R, Grady D, Fleischmann K. The prognostic value of normal exercise myocardial
perfusion imaging and exercise echocardiography: a metaanalysis. J Am Coll Cardiol 2007;49:227-37.
Geleijnse M, Elhendy A, van Domburg R, Cornel J, Rambaldi R, Salustri A, et al. Cardiac imaging for risk stratification with dobutamine-atropine stress testing in patients with
chest pain: echocardiography, perfusion scintigraphy, or
both? Circulation 1997;96:137-47.
Olmos L, Dakik H, Gordon R, Dunn J, Verani M, Quinones
M, et al. Long-term prognostic value of exercise echocardiography compared with exercise 201TI, ECG, and clinical
variables in patients evaluated for coronary artery disease.
Circulation 1998;98:2679-86.
Schinkel A, Bax J, Elhendy A, van Domburg R, Valkema R,
Vourvouri E, et al. Long-term prognostic value of dobutamine stress echocardiography compared with myocardial
perfusion scanning in patients unable to perform exercise
tests. Am J Med 2004;117:1-9.
Shaw L, Marwick T, Berman D, Sawada S, Heller G, Vasey
C, et al. Incremental cost-effectiveness of exercise echocardiography vs SPECT imaging for evaluation of stable chest
pain. Eur Heart J 2006;27:2448-58.
Ahmad M, Tianrong X, McCulloch M, Abreo G, Runge M.
Real-time three-dimensional dobutamine stress echocardiography in assessment of ischemia: comparison with twodimensional dobutamine stress echocardiography. J Am Coll
Cardiol 2001;37:1303-8.
Sugeng L, Weinert L, Lang R. Left ventricular assessment
using real-time three dimensional echocardiography. Heart
2003;89:29-36.
Yang H, Pellikka P, McCully R, Oh J, Kukuzke J, Khandheria B, et
al. Role of biplane and biplane echocardiographically guided 3-dimensional echocardiography during dobutamine stress echocardiography. J Am Soc Echocardiog 2006;19:1136-43.
Wei K, Ragosta M, Thorpe J, Coggins M, Moos S, Kaul S.
Noninvasive quantification of coronary blood flow reserve in
humans using myocardial contrast echocardiography. Circulation 2001;103:2560-5.
Masugata H, Lafitte S, Peters B, Strachan G, DeMaria A.
Comparison of real-time and intermittent triggered myocardial contrast echocardiography for quantification of coronary
stenosis severity and transmural perfusion gradient. Circulation 2001;104:1550-6.
Moir S, Haluska B, Jenkins C, Fathi R, Marwick T. Incremental benefit of myocardial contrast to combine dipyridamole-exercise stress echocardiography for the assessment
of coronary artery disease. Circulation 2004;110:1108-13.
Elhendy A, O’Leary E, Xie F, Mcgrain A, Anderson J, Porter T.
Comparative accuracy of real-time myocardial contrast perfusion
imaging and wall motion analysis during dobutamine stress echocardiography for the diagnosis of coronary artery disease. J Am Coll
Cardiol 2004;44:2185-91.